Metalloproteinases and metalloproteinase inhibitors in age-related diseases

Current Pharmaceutical Design

Volumn 20, Issue 18, 2014, Pages 2993-3018

  Gargiulo, Simona ^a   Gamba, Paola ^a   Poli, Giuseppe ^a   Leonarduzzi, Gabriella ^a  

^a UNIVERSITY OF TURIN   (Italy)

Author keywords

Atherosclerosis; Diabetes mellitus; Metalloproteinase inhibitors; Metalloproteinases; Neurodegenerative diseases; Osteoarthritis

Indexed keywords

ADAM PROTEIN; GELATINASE A; GELATINASE B; HERMES ANTIGEN; HYALURONIC ACID; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; INTERSTITIAL COLLAGENASE; MATRIX METALLOPROTEINASE 14; METALLOPROTEINASE; METALLOPROTEINASE INHIBITOR; SMALL INTERFERING RNA; STROMELYSIN; STROMELYSIN 2; STROMELYSIN 3; THROMBOSPONDIN; TISSUE INHIBITOR OF METALLOPROTEINASE; TISSUE INHIBITOR OF METALLOPROTEINASE 1; TISSUE INHIBITOR OF METALLOPROTEINASE 2; MATRIX METALLOPROTEINASE; MATRIX METALLOPROTEINASE INHIBITOR;

AGE RELATED DISEASE; ALZHEIMER DISEASE; ARTICLE; ATHEROSCLEROSIS; CHRONIC DISEASE; COGNITIVE DEFECT; DEGENERATIVE DISEASE; HUMAN; NONHUMAN; OSTEOARTHRITIS; PARKINSON DISEASE; PRIORITY JOURNAL; PROTEIN DEGRADATION; AGE; ANIMAL; DISEASE COURSE; DRUG EFFECTS; EXTRACELLULAR MATRIX; METABOLISM; PATHOLOGY; PHYSIOLOGY;

AGE FACTORS; ANIMALS; DISEASE PROGRESSION; EXTRACELLULAR MATRIX; HUMANS; MATRIX METALLOPROTEINASE INHIBITORS; MATRIX METALLOPROTEINASES; METALLOPROTEASES;

EID: 84903706776     PISSN: 13816128     EISSN: 18734286     Source Type: Journal    
DOI: 10.2174/13816128113196660701     Document Type: Article

References (502)

1. Swarnakar S, Mishra A, Chaudhuri SR. The gelatinases and their inhibitors: the structure-activity relationships. EXS 2012; 103: 57-82.
2. Weber S, Saftig P. Ectodomain shedding and ADAMs in development. Development 2012; 139: 3693-709.
3. Yong VW. Metalloproteinases: mediators of pathology and regeneration in the CNS. Nat Rev Neurosci 2005; 6: 931-44.
4. Kheradmand F, Werb Z. Shedding light on sheddases: role in growth and development. Bioessays 2002; 24: 8-12.
5. Schlöndorff J, Blobel CP. Metalloprotease-disintegrins: modular proteins capable of promoting cell-cell interactions and triggering signals by protein-ectodomain shedding. J Cell Sci 1999; 112: 3603-17.
6. Seals DF, Courtneidge SA. The ADAMs family of metalloproteases: multidomain proteins with multiple functions. Genes Dev 2003; 17: 7-30.
7. Yong VW, Power C, Forsyth P, Edwards DR. Metalloproteinases in biology and pathology of the nervous system. Nat Rev Neurosci 2001; 2: 502-11.
8. Blobel CP. Remarkable roles of proteolysis on and beyond the cell surface. Curr Opin Cell Biol 2000; 12: 606-12.
9. Alfandari D, McCusker C, Cousin H. ADAM function in embryogenesis. Semin Cell Dev Biol 2009; 20: 153-63.
10. Dreymueller D, Pruessmeyer J, Groth E, Ludwig A. The role of ADAM-mediated shedding in vascular biology. Eur J Cell Biol 2012; 91: 472-85.
11. Marcinkiewicz M, Seidah NG. Coordinated expression of betaamyloid precursor protein and the putative beta-secretase BACE and alpha-secretase ADAM10 in mouse and human brain. J Neurochem 2000; 75: 2133-43.
12. Kärkkäinen I, Rybnikova E, Pelto-Huikko M, Huovila AP. Metalloprotease-disintegrin (ADAM) genes are widely and differentially expressed in the adult CNS. Mol Cell Neurosci 2000; 15: 547-60.
13. Dallas DJ, Genever PG, Patton AJ, Millichip MI, McKie N, Skerry TM. Localization of ADAM10 and Notch receptors in bone. Bone 1999; 25: 9-15.
14. McKie N, Edwards T, Dallas DJ. Expression of members of a novel membrane linked metalloproteinase family (ADAM) in human articular chondrocytes. Biochem Biophys Res Commun 1997; 230: 335-9.
15. Huang K, Wu LD. Aggrecanase and aggrecan degradation in osteoarthritis: a review. J Int Med Res 2008; 36: 1149-60.
16. Troeberg L, Nagase H. Proteases involved in cartilage matrix degradation in osteoarthritis. Biochim Biophys Acta 2012; 1824: 133-45.
17. Limb GA, Matter K, Murphy G, et al. Matrix metalloproteinase-1 associates with intracellular organelles and confers resistance to lamin A/C degradation during apoptosis. Am J Pathol 2005; 166: 1555-63.
18. Kwan JA, Schulze CJ, Wang W, et al. Matrix metalloproteinase-2 (MMP-2) is present in the nucleus of cardiac myocytes and is capable of cleaving poly (ADP-ribose) polymerase (PARP) in vitro. FASEB J 2004; 18: 690-2.
19. Luo D, Mari B, Stoll I, Anglard P. Alternative splicing and promoter usage generates an intracellular stromelysin 3 isoform directly translated as an active matrix metalloproteinase. J Biol Chem 2002; 277: 25527-36.
20. Newby AC. Dual role of matrix metalloproteinases (matrixins) in intimal thickening and atherosclerotic plaque rupture. Physiol Rev 2005; 85: 1-31.
21. Nagase H, Visse R, Murphy G. Structure and function of matrix metalloproteinases and TIMPs. Cardiovasc Res 2006; 69: 562-73.
22. Sternlicht MD, Werb Z. How matrix metalloproteinases regulate cell behavior. Annu Rev Cell Dev Biol 2001; 17: 463-516.
23. Rosenberg GA. Matrix metalloproteinases in neuroinflammation. Glia 2002; 39: 279-91.
24. Mott JD, Werb Z. Regulation of matrix biology by matrix metalloproteinases. Curr Opin Cell Biol 2004; 16: 558-64.
25. Parks WC, Wilson CL, López-Boado YS. Matrix metalloproteinases as modulators of inflammation and innate immunity. Nat Rev Immunol 2004; 4: 617-29.
26. Egeblad M, Werb Z. New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer 2002; 2: 161-74.
27. Cauwe B, Van den Steen PE, Opdenakker G. The biochemical, biological, and pathological kaleidoscope of cell surface substrates processed by matrix metalloproteinases. Crit Rev Biochem Mol Biol 2007; 42: 113-85.
28. Vargová V, Pytliak M, Mechírová V. Matrix metalloproteinases. EXS 2012; 103: 1-33.
29. Agrawal SM, Lau L, Yong VW. MMPs in the central nervous system: where the good guys go bad. Semin Cell Dev Biol 2008; 19: 42-51.
30. Visse R, Nagase H. Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry. Circ Res 2003; 92: 827-39.
31. Rajagopalan S, Meng XP, Ramasamy S, Harrison DG, Galis ZS. Reactive oxygen species produced by macrophage-derived foam cells regulate the activity of vascular matrix metalloproteinases in vitro. Implications for atherosclerotic plaque stability. J Clin Invest 1996; 98: 2572-9.
32. Gu Z, Kaul M, Yan B, et al. S-nitrosylation of matrix metalloproteinases: signaling pathway to neuronal cell death. Science 2002; 297: 1186-90.
33. Carmeliet P, Moons L, Herbert JM, et al. Urokinase but not tissue plasminogen activator mediates arterial neointima formation in mice. Circ Res 1997; 81: 829-39.
34. Browatzki M, Larsen D, Pfeiffer CA, et al. Angiotensin II stimulates matrix metalloproteinase secretion in human vascular smooth muscle cells via nuclear factor-kappaB and activator protein 1 in a redox-sensitive manner. J Vasc Res 2005; 42: 415-23.
35. Death AK, Fisher EJ, McGrath KC, Yue DK. High glucose alters matrix metalloproteinase expression in two key vascular cells: potential impact on atherosclerosis in diabetes. Atherosclerosis 2003; 168: 263-9.
36. Nelson AR, Fingleton B, Rothenberg ML, Matrisian LM. Matrix metalloproteinases: biologic activity and clinical implications. J Clin Oncol 2000; 18: 1135-49.
37. Chakraborti S, Mandal M, Das S, Mandal A, Chakraborti T. Regulation of matrix metalloproteinases: an overview. Mol Cell Biochem 2003; 253: 269-85.
38. Schmidt R, Bültmann A, Ungerer M, et al. Extracellular matrix metalloproteinase inducer regulates matrix metalloproteinase activity in cardiovascular cells: implications in acute myocardial infarction. Circulation 2006; 113: 834-41.
39. Yoon YW, Kwon HM, Hwang KC, et al. Upstream regulation of matrix metalloproteinase by EMMPRIN; extracellular matrix metalloproteinase inducer in advanced atherosclerotic plaque. Atherosclerosis 2005; 180: 37-44.
40. Cawston TE, Mercer E. Preferential binding of collagenase to alpha 2-macroglobulin in the presence of the tissue inhibitor of metalloproteinases. FEBS Lett 1986; 209: 9-12.
41. Baker AH, Edwards DR, Murphy G. Metalloproteinase inhibitors: biological actions and therapeutic opportunities. J Cell Sci 2002; 115: 3719-27.
42. Brew K, Dinakarpandian D, Nagase H. Tissue inhibitors of metalloproteinases: evolution, structure and function. Biochim Biophys Acta 2000; 1477: 267-83.
43. Amour A, Slocombe PM, Webster A, et al. TNF-alpha converting enzyme (TACE) is inhibited by TIMP-3. FEBS Lett 1998; 435: 39-44.
44. Higashi S, Miyazaki K. Identification of a region of beta-amyloid precursor protein essential for its gelatinase A inhibitory activity. J Biol Chem 2003; 278: 14020-8.
45. Mott JD, Thomas CL, Rosenbach MT, Takahara K, Greenspan DS, Banda MJ. Post-translational proteolytic processing of procollagen C-terminal proteinase enhancer releases a metalloproteinase inhibitor. J Biol Chem 2000; 275: 1384-90.
46. Oh J, Takahashi R, Kondo S, et al. The membrane-anchored MMP inhibitor RECK is a key regulator of extracellular matrix integrity and angiogenesis. Cell 2001; 107: 789-800.
47. Mauviel A. Cytokine regulation of metalloproteinase gene expression. J Cell Biochem 1993; 53: 288-95.
48. Spinale FG. Matrix metalloproteinases: regulation and dysregulation in the failing heart. Circ Res 2002; 90: 520-30.
49. Newby AC. Metalloproteinases and vulnerable atherosclerotic plaques. Trends Cardiovasc Med 2007; 17: 253-8.
50. Raffetto JD, Khalil RA. Matrix metalloproteinases and their inhibitors in vascular remodeling and vascular disease. Biochem Pharmacol 2008; 75: 346-59.
51. Busti C, Falcinelli E, Momi S, Gresele P. Matrix metalloproteinases and peripheral arterial disease. Intern Emerg Med 2010; 5: 13-25.
52. Ye S. Influence of matrix metalloproteinase genotype on cardiovascular disease susceptibility and outcome. Cardiovasc Res 2006; 69: 636-45.
53. Ghaderian SM, Akbarzadeh Najar R, Tabatabaei Panah AS. Genetic polymorphisms and plasma levels of matrix metalloproteinases and their relationships with developing acute myocardial infarction. Coron Artery Dis 2010; 21: 330-5.
54. Kunz J. Matrix metalloproteinases and atherogenesis in dependence of age. Gerontology 2007; 53: 63-73.
55. Romanic AM, Harrison SM, Bao W, et al. Myocardial protection from ischemia/reperfusion injury by targeted deletion of matrix metalloproteinase-9. Cardiovasc Res 2002; 54: 549-58.
56. Matsumura S, Iwanaga S, Mochizuki S, Okamoto H, Ogawa S, Okada Y. Targeted deletion or pharmacological inhibition of MMP-2 prevents cardiac rupture after myocardial infarction in mice. J Clin Invest 2005; 115: 599-609.
57. Longo GM, Xiong W, Greiner TC, Zhao Y, Fiotti N, Baxter BT. Matrix metalloproteinases 2 and 9 work in concert to produce aortic aneurysms. J Clin Invest 2002; 110: 625-32.
58. Galt SW, Lindemann S, Allen L, et al. Outside-in signals delivered by matrix metalloproteinase-1 regulate platelet function. Circ Res 2002; 90: 1093-9.
59. Sawicki G, Sanders EJ, Salas E, Wozniak M, Rodrigo J, Radomski MW. Localization and translocation of MMP-2 during aggregation of human platelets. Thromb Haemost 1998; 80: 836-9.
60. Fedak PW, Smookler DS, Kassiri Z, et al. TIMP-3 deficiency leads to dilated cardiomyopathy. Circulation 2004; 110: 2401-9.
61. Insull W Jr. The pathology of atherosclerosis: plaque development and plaque responses to medical treatment. Am J Med 2009; 122: S3-14.
62. Loftus I, Thompson M. Plaque biology: interesting science or pharmacological treasure trove? Eur J Vasc Endovasc Surg 2008; 36: 507-16.
63. Aikawa M, Libby P. The vulnerable atherosclerotic plaque: pathogenesis and therapeutic approach. Cardiovasc Pathol 2004; 13: 125-38.
64. Virmani R, Kolodgie FD, Burke AP, Farb A, Schwartz SM. Lessons from sudden coronary death: a comprehensive morphological classification scheme for atherosclerotic lesions. Arterioscler Thromb Vasc Biol 2000; 20: 1262-75.
65. Virmani R, Burke AP, Farb A, Kolodgie FD. Pathology of the vulnerable plaque. J Am Coll Cardiol 2006; 47: C13-8.
66. Halvorsen B, Otterdal K, Dahl TB, et al. Atherosclerotic plaque stability--what determines the fate of a plaque? Prog Cardiovasc Dis 2008; 51: 183-94.
67. Buffon A, Biasucci LM, Liuzzo G, D'Onofrio G, Crea F, Maseri A. Widespread coronary inflammation in unstable angina. N Engl J Med 2002; 347: 5-12.
68. Clarke MC, Figg N, Maguire JJ, et al. Apoptosis of vascular smooth muscle cells induces features of plaque vulnerability in atherosclerosis. Nat Med 2006; 12: 1075-80.
69. Tabas I. Consequences and therapeutic implications of macrophage apoptosis in atherosclerosis: the importance of lesion stage and phagocytic efficiency. Arterioscler Thromb Vasc Biol 2005; 25: 2255-64.
70. Dickson BC, Gotlieb AI. Towards understanding acute destabilization of vulnerable atherosclerotic plaques. Cardiovasc Pathol 2003; 12: 237-48.
71. Lutgens E, van Suylen RJ, Faber BC, et al. Atherosclerotic plaque rupture: local or systemic process? Arterioscler Thromb Vasc Biol 2003; 23: 2123-30.
72. Nakamura M, Lee DP, Yeung AC. Identification and treatment of vulnerable plaque. Rev Cardiovasc Med 2004; 2: S22-33.
73. Wang LX, Lü SZ, Zhang WJ, Song XT, Chen H, Zhang LJ. Coronary spasm, a pathogenic trigger of vulnerable plaque rupture. Chin Med J (Engl) 2011; 124: 4071-8.
74. Gijsen F, van der Giessen A, van der Steen A, Wentzel J. Shear stress and advanced atherosclerosis in human coronary arteries. J Biomech 2013; 46: 240-7.
75. Toutouzas K, Synetos A, Nikolaou C, Tsiamis E, Tousoulis D, Stefanadis C. Matrix metalloproteinases and vulnerable atheromatous plaque. Curr Top Med Chem 2012; 12: 1166-80.
76. Loftus IM, Naylor AR, Bell PR, Thompson MM. Matrix metalloproteinases and atherosclerotic plaque instability. Br J Surg 2002; 89: 680-94.
77. Bäck M, Ketelhuth DF, Agewall S. Matrix metalloproteinases in atherothrombosis. Prog Cardiovasc Dis 2010; 52: 410-28.
78. Newby AC. Metalloproteinase expression in monocytes and macrophages and its relationship to atherosclerotic plaque instability. Arterioscler Thromb Vasc Biol 2008; 28: 2108-14.
79. Reel B, Sala-Newby GB, Huang WC, Newby AC. Diverse patterns of cyclooxygenase-independent metalloproteinase gene regulation in human monocytes. Br J Pharmacol 2011; 163: 1679-90.
80. Amorino GP, Hoover RL. Interactions of monocytic cells with human endothelial cells stimulate monocytic metalloproteinase production. Am J Pathol 1998; 152: 199-207.
81. Galt SW, Lindemann S, Medd D, et al. Differential regulation of matrix metalloproteinase-9 by monocytes adherent to collagen and platelets. Circ Res 2001; 89: 509-16.
82. Galis ZS, Sukhova GK, Kranzhöfer R, Clark S, Libby P. Macrophage foam cells from experimental atheroma constitutively produce matrix-degrading proteinases. Proc Natl Acad Sci USA 1995; 92: 402-6.
83. Chase AJ, Bond M, Crook MF, Newby AC. Role of nuclear factorkappa B activation in metalloproteinase-1,-3, and-9 secretion by human macrophages in vitro and rabbit foam cells produced in vivo. Arterioscler Thromb Vasc Biol 2002; 22: 765-71.
84. Feinberg MW, Jain MK, Werner F, et al. Transforming growth factor-beta 1 inhibits cytokine-mediated induction of human metalloelastase in macrophages. J Biol Chem 2000; 275: 25766-73.
85. Mach F, Schönbeck U, Bonnefoy JY, Pober JS, Libby P. Activation of monocyte/macrophage functions related to acute atheroma complication by ligation of CD40: induction of collagenase, stromelysin, and tissue factor. Circulation 1997; 96: 396-9.
86. Schönbeck U, Mach F, Sukhova GK, et al. Expression of stromelysin-3 in atherosclerotic lesions: regulation via CD40-CD40 ligand signaling in vitro and in vivo. J Exp Med 1999; 189: 843-53.
87. Wu L, Fan J, Matsumoto Si, Watanabe T. Induction and regulation of matrix metalloproteinase-12 by cytokines and CD40 signaling in monocyte/macrophages. Biochem Biophys Res Commun 2000; 269: 808-15.
88. Herman MP, Sukhova GK, Libby P, et al. Expression of neutrophil collagenase (matrix metalloproteinase-8) in human atheroma: a novel collagenolytic pathway suggested by transcriptional profiling. Circulation 2001; 104: 1899-904.
89. Moreau M, Brocheriou I, Petit L, Ninio E, Chapman MJ, Rouis M. Interleukin-8 mediates downregulation of tissue inhibitor of metalloproteinase-1 expression in cholesterol-loaded human macrophages: relevance to stability of atherosclerotic plaque. Circulation 1999; 99: 420-6.
90. George SJ, Zaltsman AB, Newby AC. Surgical preparative injury and neointima formation increase MMP-9 expression and MMP-2 activation in human saphenous vein. Cardiovasc Res 1997; 33: 447-59.
91. Johnson JL, van Eys GJ, Angelini GD, George SJ. Injury induces dedifferentiation of smooth muscle cells and increased matrixdegrading metalloproteinase activity in human saphenous vein. Arterioscler Thromb Vasc Biol 2001; 21: 1146-51.
92. Galis ZS, Muszynski M, Sukhova GK, et al. Cytokine-stimulated human vascular smooth muscle cells synthesize a complement of enzymes required for extracellular matrix digestion. Circ Res 1994; 75: 181-9.
93. Fabunmi RP, Baker AH, Murray EJ, Booth RF, Newby AC. Divergent regulation by growth factors and cytokines of 95 kDa and 72 kDa gelatinases and tissue inhibitors or metalloproteinases-1,-2, and-3 in rabbit aortic smooth muscle cells. Biochem J 1996; 315: 335-42.
94. Bond M, Chase AJ, Baker AH, Newby AC. Inhibition of transcription factor NF-kappaB reduces matrix metalloproteinase-1,-3 and-9 production by vascular smooth muscle cells. Cardiovasc Res 2001; 50: 556-65.
95. Schönbeck U, Mach F, Sukhova GK, et al. Regulation of matrix metalloproteinase expression in human vascular smooth muscle cells by T lymphocytes: a role for CD40 signaling in plaque rupture? Circ Res 1997; 81: 448-54.
96. Galis ZS, Sukhova GK, Lark MW, Libby P. Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques. J Clin Invest 1994; 94: 2493-503.
97. Yakubenko VP, Lobb RR, Plow EF, Ugarova TP. Differential induction of gelatinase B (MMP-9) and gelatinase A (MMP-2) in T lymphocytes upon alpha(4)beta(1)-mediated adhesion to VCAM-1 and the CS-1 peptide of fibronectin. Exp Cell Res 2000; 260: 73-84.
98. Baram D, Vaday GG, Salamon P, Drucker I, Hershkoviz R, Mekori YA. Human mast cells release metalloproteinase-9 on contact with activated T cells: juxtacrine regulation by TNF-alpha. J Immunol 2001; 167: 4008-16.
99. Hanemaaijer R, Koolwijk P, le Clercq L, de Vree WJ, van Hinsbergh VW. Regulation of matrix metalloproteinase expression in human vein and microvascular endothelial cells. Effects of tumour necrosis factor alpha, interleukin 1 and phorbol ester. Biochem J 1993; 296: 803-9.
100. Hojo Y, Ikeda U, Takahashi M, et al. Matrix metalloproteinase-1 expression by interaction between monocytes and vascular endothelial cells. J Mol Cell Cardiol 2000; 32: 1459-68.
101. Newby AC. Matrix metalloproteinase inhibition therapy for vascular diseases. Vascul Pharmacol 2012; 56: 232-44.
102. Mach F, Schönbeck U, Fabunmi RP, et al. T lymphocytes induce endothelial cell matrix metalloproteinase expression by a CD40Ldependent mechanism: implications for tubule formation. Am J Pathol 1999; 154: 229-38.
103. Huang Y, Song L, Wu S, Fan F, Lopes-Virella MF. Oxidized LDL differentially regulates MMP-1 and TIMP-1 expression in vascular endothelial cells. Atherosclerosis 2001; 156: 119-25.
104. Santos-Martínez MJ, Medina C, Jurasz P, Radomski MW. Role of metalloproteinases in platelet function. Thromb Res 2008; 121: 535-42.
105. Gresele P, Falcinelli E, Momi S. Potentiation and priming of platelet activation: a potential target for antiplatelet therapy. Trends Pharmacol Sci 2008; 29: 352-60.
106. Xu XP, Meisel SR, Ong JM, et al. Oxidized low-density lipoprotein regulates matrix metalloproteinase-9 and its tissue inhibitor in human monocyte-derived macrophages. Circulation 1999; 99: 993-8.
107. Rajavashisth TB, Xu XP, Jovinge S, et al. Membrane type 1 matrix metalloproteinase expression in human atherosclerotic plaques: evidence for activation by proinflammatory mediators. Circulation 1999; 99: 3103-9.
108. Huang Y, Mironova M, Lopes-Virella MF. Oxidized LDL stimulates matrix metalloproteinase-1 expression in human vascular endothelial cells. Arterioscler Thromb Vasc Biol 1999; 19: 2640-7.
109. Silence J, Collen D, Lijnen HR. Reduced atherosclerotic plaque but enhanced aneurysm formation in mice with inactivation of the tissue inhibitor of metalloproteinase-1 (TIMP-1) gene. Circ Res 2002; 90: 897-903.
110. Lemaître V, Soloway PD, D'Armiento J. Increased medial degradation with pseudo-aneurysm formation in apolipoprotein E-knockout mice deficient in tissue inhibitor of metalloproteinases-1. Circulation 2003; 107: 333-8.
111. Gough PJ, Gomez IG, Wille PT, Raines EW. Macrophage expression of active MMP-9 induces acute plaque disruption in apoEdeficient mice. J Clin Invest 2006; 116: 59-69.
112. de Nooijer R, Verkleij CJ, von der Thüsen JH, et al. Lesional overexpression of matrix metalloproteinase-9 promotes intraplaque hemorrhage in advanced lesions but not at earlier stages of atherogenesis. Arterioscler Thromb Vasc Biol 2006; 26: 340-6.
113. Lemaître V, O'Byrne TK, Borczuk AC, Okada Y, Tall AR, D'Armiento J. ApoE knockout mice expressing human matrix metalloproteinase-1 in macrophages have less advanced atherosclerosis. J Clin Invest 2001; 107: 1227-34.
114. Fukumoto Y, Deguchi JO, Libby P, et al. Genetically determined resistance to collagenase action augments interstitial collagen accumulation in atherosclerotic plaques. Circulation 2004; 110: 1953-9.
115. Deguchi JO, Aikawa E, Libby P, et al. Matrix metalloproteinase-13/collagenase-3 deletion promotes collagen accumulation and organization in mouse atherosclerotic plaques. Circulation 2005; 112: 2708-15.
116. Kuzuya M, Nakamura K, Sasaki T, Cheng XW, Itohara S, Iguchi A. Effect of MMP-2 deficiency on atherosclerotic lesion formation in apoE-deficient mice. Arterioscler Thromb Vasc Biol 2006; 26: 1120-5.
117. Silence J, Lupu F, Collen D, Lijnen HR. Persistence of atherosclerotic plaque but reduced aneurysm formation in mice with stromelysin-1 (MMP-3) gene inactivation. Arterioscler Thromb Vasc Biol 2001; 21: 1440-5.
118. Luttun A, Lutgens E, Manderveld A, et al. Loss of matrix metalloproteinase-9 or matrix metalloproteinase-12 protects apolipoprotein E-deficient mice against atherosclerotic media destruction but differentially affects plaque growth. Circulation 2004; 109: 1408-14.
119. Johnson JL, George SJ, Newby AC, Jackson CL. Divergent effects of matrix metalloproteinases 3, 7, 9, and 12 on atherosclerotic plaque stability in mouse brachiocephalic arteries. Proc Natl Acad Sci USA 2005; 102: 15575-80.
120. Johnson JL, Dwivedi A, Somerville M, George SJ, Newby AC. Matrix metalloproteinase (MMP)-3 activates MMP-9 mediated vascular smooth muscle cell migration and neointima formation in mice. Arterioscler Thromb Vasc Biol 2011; 31: e35-44.
121. Williams H, Johnson JL, Jackson CL, White SJ, George SJ. MMP-7 mediates cleavage of N-cadherin and promotes smooth muscle cell apoptosis. Cardiovasc Res 2010; 87: 137-46.
122. Johnson JL, Devel L, Czarny B, et al. A selective matrix metalloproteinase-12 inhibitor retards atherosclerotic plaque development in apolipoprotein E-knockout mice. Arterioscler Thromb Vasc Biol 2011; 31: 528-35.
123. Liang J, Liu E, Yu Y, et al. Macrophage metalloelastase accelerates the progression of atherosclerosis in transgenic rabbits. Circulation 2006; 113: 1993-2001.
124. Laxton RC, Hu Y, Duchene J, et al. A role of matrix metalloproteinase-8 in atherosclerosis. Circ Res 2009; 105: 921-9.
125. Schneider F, Sukhova GK, Aikawa M, et al. Matrixmetalloproteinase-14 deficiency in bone-marrow-derived cells promotes collagen accumulation in mouse atherosclerotic plaques. Circulation 2008; 117: 931-9.
126. Galis ZS, Khatri JJ. Matrix metalloproteinases in vascular remodeling and atherogenesis: the good, the bad, and the ugly. Circ Res 2002; 90: 251-62.
127. Newby AC. Matrix metalloproteinases regulate migration, proliferation, and death of vascular smooth muscle cells by degrading matrix and non-matrix substrates. Cardiovasc Res 2006; 69: 614-24.
128. Cho A, Reidy MA. Matrix metalloproteinase-9 is necessary for the regulation of smooth muscle cell replication and migration after arterial injury. Circ Res 2002; 91: 845-51.
129. Galis ZS, Johnson C, Godin D, et al. Targeted disruption of the matrix metalloproteinase-9 gene impairs smooth muscle cell migration and geometrical arterial remodeling. Circ Res 2002; 91: 852-9.
130. Choi ET, Collins ET, Marine LA, et al. Matrix metalloproteinase-9 modulation by resident arterial cells is responsible for injuryinduced accelerated atherosclerotic plaque development in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 2005; 25: 1020-5.
131. Filippov S, Koenig GC, Chun TH, et al. MT1-matrix metalloproteinase directs arterial wall invasion and neointima formation by vascular smooth muscle cells. J Exp Med 2005; 202: 663-71.
132. Wu YJ, Bond M, Sala-Newby GB, Newby AC. Altered S-phase kinase-associated protein-2 levels are a major mediator of cyclic nucleotide-induced inhibition of vascular smooth muscle cell proliferation. Circ Res 2006; 98: 1141-50.
133. Johnson JL, Baker AH, Oka K, et al. Suppression of atherosclerotic plaque progression and instability by tissue inhibitor of metalloproteinase-2: involvement of macrophage migration and apoptosis. Circulation 2006; 113: 2435-44.
134. Johnson JL, Fritsche-Danielson R, Behrendt M, et al. Effect of broad-spectrum matrix metalloproteinase inhibition on atherosclerotic plaque stability. Cardiovasc Res 2006; 71: 586-95.
135. Tedgui A, Mallat Z. Cytokines in atherosclerosis: pathogenic and regulatory pathways. Physiol Rev 2006; 86: 515-81.
136. Katsuda S, Kaji T. Atherosclerosis and extracellular matrix. J Atheroscler Thromb 2003; 10: 267-74.
137. Choudhary S, Higgins CL, Chen IY, et al. Quantitation and localization of matrix metalloproteinases and their inhibitors in human carotid endarterectomy tissues. Arterioscler Thromb Vasc Biol 2006; 26: 2351-8.
138. Sluijter JP, Pulskens WP, Schoneveld AH, et al. Matrix metalloproteinase 2 is associated with stable and matrix metalloproteinases 8 and 9 with vulnerable carotid atherosclerotic lesions: a study in human endarterectomy specimen pointing to a role for different extracellular matrix metalloproteinase inducer glycosylation forms. Stroke 2006; 37: 235-9.
139. Sukhova GK, Schönbeck U, Rabkin E, et al. Evidence for increased collagenolysis by interstitial collagenases-1 and-3 in vulnerable human atheromatous plaques. Circulation 1999; 99: 2503-9.
140. Monaco C, Gregan SM, Navin TJ, Foxwell BM, Davies AH, Feldmann M. Toll-like receptor-2 mediates inflammation and matrix degradation in human atherosclerosis. Circulation 2009; 120: 2462-9.
141. Thomas AC, Sala-Newby GB, Ismail Y, Johnson JL, Pasterkamp G, Newby AC. Genomics of foam cells and nonfoamy macrophages from rabbits identifies arginase-I as a differential regulator of nitric oxide production. Arterioscler Thromb Vasc Biol 2007; 27: 571-7.
142. Johnson JL, Sala-Newby GB, Ismail Y, Aguilera CM, Newby AC. Low tissue inhibitor of metalloproteinases 3 and high matrix metalloproteinase 14 levels defines a subpopulation of highly invasive foam-cell macrophages. Arterioscler Thromb Vasc Biol 2008; 28: 1647-53.
143. Ikeda U, Shimada K. Matrix metalloproteinases and coronary artery diseases. Clin Cardiol 2003; 26: 55-9.
144. Orbe J, Fernandez L, Rodríguez JA, et al. Different expression of MMPs/TIMP-1 in human atherosclerotic lesions. Relation to plaque features and vascular bed. Atherosclerosis 2003; 170: 269-76.
145. Noji Y, Kajinami K, Kawashiri MA, et al. Circulating matrix metalloproteinases and their inhibitors in premature coronary atherosclerosis. Clin Chem Lab Med 2001; 39: 380-4.
146. Beaudeux JL, Giral P, Bruckert E, Bernard M, Foglietti MJ, Chapman MJ. Serum matrix metalloproteinase-3 and tissue inhibitor of metalloproteinases-1 as potential markers of carotid atherosclerosis in infraclinical hyperlipidemia. Atherosclerosis 2003; 169: 139-46.
147. Partridge CR, Hawker JR Jr, Forough R. Overexpression of a secretory form of FGF-1 promotes MMP-1-mediated endothelial cell migration. J Cell Biochem 2000; 78: 487-99.
148. Holnthoner W, Kerenyi M, Gröger M, Kratochvill F, Petzelbauer P. Regulation of matrilysin expression in endothelium by fibroblast growth factor-2. Biochem Biophys Res Commun 2006; 342: 725-33.
149. Burbridge MF, Cogé F, Galizzi JP, Boutin JA, West DC, Tucker GC. The role of the matrix metalloproteinases during in vitro vessel formation. Angiogenesis 2002; 5: 215-26.
150. Duhamel-Clérin E, Orvain C, Lanza F, Cazenave JP, Klein-Soyer C. Thrombin receptor-mediated increase of two matrix metalloproteinases, MMP-1 and MMP-3, in human endothelial cells. Arterioscler Thromb Vasc Biol 1997; 17: 1931-8.
151. Lafleur MA, Hollenberg MD, Atkinson SJ, Knäuper V, Murphy G, Edwards DR. Activation of pro-(matrix metalloproteinase-2) (pro-MMP-2) by thrombin is membrane-type-MMP-dependent in human umbilical vein endothelial cells and generates a distinct 63 kDa active species. Biochem J 2001; 357: 107-15.
152. Rybakowski JK. Matrix metalloproteinase-9 (MMP9)-A mediating enzyme in cardiovascular disease, cancer, and neuropsychiatric disorders. Cardiovasc Psychiatry Neurol 2009; 2009: 904836.
153. Pöllänen PJ, Karhunen PJ, Mikkelsson J, et al. Coronary artery complicated lesion area is related to functional polymorphism of matrix metalloproteinase 9 gene: an autopsy study. Arterioscler Thromb Vasc Biol 2001; 21: 1446-50.
154. Morgan AR, Zhang B, Tapper W, Collins A, Ye S. Haplotypic analysis of the MMP-9 gene in relation to coronary artery disease. J Mol Med (Berl) 2003; 81: 321-6.
155. Blankenberg S, Rupprecht HJ, Poirier O, et al. Plasma concentrations and genetic variation of matrix metalloproteinase 9 and prognosis of patients with cardiovascular disease. Circulation 2003; 107: 1579-85.
156. Johnson C, Galis ZS. Matrix metalloproteinase-2 and-9 differentially regulate smooth muscle cell migration and cell-mediated collagen organization. Arterioscler Thromb Vasc Biol 2004; 24: 54-60.
157. Loftus IM, Naylor AR, Goodall S, et al. Increased matrix metalloproteinase-9 activity in unstable carotid plaques. A potential role in acute plaque disruption. Stroke 2000; 31: 40-7.
158. Chen F, Eriksson P, Hansson GK, et al. Expression of matrix metalloproteinase 9 and its regulators in the unstable coronary atherosclerotic plaque. Int J Mol Med 2005; 15: 57-65.
159. Brown DL, Hibbs MS, Kearney M, Loushin C, Isner JM. Identification of 92-kD gelatinase in human coronary atherosclerotic lesions. Association of active enzyme synthesis with unstable angina. Circulation 1995; 91: 2125-31.
160. Hojo Y, Ikeda U, Katsuki Ta, Mizuno O, Fujikawa H, Shimada K. Matrix metalloproteinase expression in the coronary circulation induced by coronary angioplasty. Atherosclerosis 2002; 161: 185-92.
161. Mathapati S, Arumugam SB, Verma RS. High cholesterol diet increases MMP9 and CD40 immunopositivity in early atherosclerotic plaque in rabbits. Acta Histochem 2010; 112: 618-23.
162. Fukuda D, Shimada K, Tanaka A, et al. Comparison of levels of serum matrix metalloproteinase-9 in patients with acute myocardial infarction versus unstable angina pectoris versus stable angina pectoris. Am J Cardiol 2006; 97: 175-80.
163. Alvarez B, Ruiz C, Chacón P, Alvarez-Sabin J, Matas M. Serum values of metalloproteinase-2 and metalloproteinase-9 as related to unstable plaque and inflammatory cells in patients with greater than 70% carotid artery stenosis. J Vasc Surg 2004; 40: 469-75.
164. Eldrup N, Grønholdt ML, Sillesen H, Nordestgaard BG. Elevated matrix metalloproteinase-9 associated with stroke or cardiovascular death in patients with carotid stenosis. Circulation 2006; 114: 1847-54.
165. Jefferis BJ, Whincup P, Welsh P, et al. Prospective study of matrix metalloproteinase-9 and risk of myocardial infarction and stroke in older men and women. Atherosclerosis 2010; 208: 557-63.
166. Ferroni P, Basili S, Martini F, et al. Serum metalloproteinase 9 levels in patients with coronary artery disease: a novel marker of inflammation. J Investig Med 2003; 51: 295-300.
167. Konstantino Y, Nguyen TT, Wolk R, Aiello RJ, Terra SG, Fryburg DA. Potential implications of matrix metalloproteinase-9 in assessment and treatment of coronary artery disease. Biomarkers 2009; 14: 118-29.
168. Li L, Renier G. The oral anti-diabetic agent, gliclazide, inhibits oxidized LDL-mediated LOX-1 expression, metalloproteinase-9 secretion and apoptosis in human aortic endothelial cells. Atherosclerosis 2009; 204: 40-6.
169. Hua Y, Xue J, Sun F, Zhu L, Xie M. Aspirin inhibits MMP-2 and MMP-9 expressions and activities through upregulation of PPARalpha/gamma and TIMP gene expressions in ox-LDLstimulated macrophages derived from human monocytes. Pharmacology 2009; 83: 18-25.
170. Kang JH, Kim JK, Park WH, et al. Ascochlorin suppresses oxLDLinduced MMP-9 expression by inhibiting the MEK/ERK signaling pathway in human THP-1 macrophages. J Cell Biochem 2007; 102: 506-14.
171. Kalela A, Koivu TA, Höyhtyä M, et al. Association of serum MMP-9 with autoantibodies against oxidized LDL. Atherosclerosis 2002; 160: 161-5.
172. Garenc C, Julien P, Levy E. Oxysterols in biological systems: the gastrointestinal tract, liver, vascular wall and central nervous system. Free Radic Res 2010; 44: 47-73.
173. Leonarduzzi G, Poli G, Sottero B, Biasi F. Activation of the mitochondrial pathway of apoptosis by oxysterols. Front Biosci 2007; 12: 791-9.
174. Sottero B, Gamba P, Gargiulo S, Leonarduzzi G, Poli G. Cholesterol oxidation products and disease: an emerging topic of interest in medicinal chemistry. Curr Med Chem 2009; 16: 685-705.
175. Poli G, Sottero B, Gargiulo S, Leonarduzzi G. Cholesterol oxidation products in the vascular remodeling due to atherosclerosis. Mol Aspects Med 2009; 30: 180-9.
176. Leonarduzzi G, Gamba P, Sottero B, et al. Oxysterol-induced upregulation of MCP-1 expression and synthesis in macrophage cells. Free Radic Biol Med 2005; 39: 1152-61.
177. Leonarduzzi G, Vizio B, Sottero B, et al. Early involvement of ROS overproduction in apoptosis induced by 7-ketocholesterol. Antioxid Redox Signal 2006; 8: 375-80.
178. Leonarduzzi G, Gamba P, Gargiulo S, et al. Oxidation as a crucial reaction for cholesterol to induce tissue degeneration: CD36 overexpression in human promonocytic cells treated with a biologically relevant oxysterol mixture. Aging Cell 2008; 7: 375-82.
179. Leonarduzzi G, Gargiulo S, Gamba P, et al. Molecular signaling operated by a diet-compatible mixture of oxysterols in upregulating CD36 receptor in CD68 positive cells. Mol Nutr Food Res 2010; 54: S31-41.
180. Gargiulo S, Sottero B, Gamba P, Chiarpotto E, Poli G, Leonarduzzi G. Plaque oxysterols induce unbalanced up-regulation of matrix metalloproteinase-9 in macrophagic cells through redox-sensitive signaling pathways: Implications regarding the vulnerability of atherosclerotic lesions. Free Radic Biol Med 2011; 51: 844-55.
181. Lim CS, Shalhoub J, Gohel MS, Shepherd AC, Davies AH. Matrix metalloproteinases in vascular disease--a potential therapeutic target? Curr Vasc Pharmacol 2010; 8: 75-85.
182. Upchurch GR Jr, Ford JW, Weiss SJ, et al. Nitric oxide inhibition increases matrix metalloproteinase-9 expression by rat aortic smooth muscle cells in vitro. J Vasc Surg 2001; 34: 76-83.
183. Uría JA, Jiménez MG, Balbín M, Freije JM, López-Otín C. Differential effects of transforming growth factor-beta on the expression of collagenase-1 and collagenase-3 in human fibroblasts. J Biol Chem 1998; 273: 9769-77.
184. Grzela T, Brawura-Biskupski-Samaha R, Jelenska MM, Szmidt J. Low molecular weight heparin treatment decreases MMP-9 plasma activity in patients with abdominal aortic aneurysm. Eur J Vasc Endovasc Surg 2008; 35: 159-61.
185. Schieffer B, Bünte C, Witte J, et al. Comparative effects of AT1-antagonism and angiotensin-converting enzyme inhibition on markers of inflammation and platelet aggregation in patients with coronary artery disease. J Am Coll Cardiol 2004; 44: 362-8.
186. Yamamoto D, Takai S, Miyazaki M. Inhibitory profiles of captopril on matrix metalloproteinase-9 activity. Eur J Pharmacol 2008; 588: 277-9.
187. Galis ZS, Asanuma K, Godin D, Meng X. N-acetyl-cysteine decreases the matrix-degrading capacity of macrophage-derived foam cells: new target for antioxidant therapy? Circulation 1998; 97: 2445-53.
188. Lutgens E, Gorelik L, Daemen MJ, et al. Requirement for CD154 in the progression of atherosclerosis. Nat Med 1999; 5: 1313-6.
189. Miralles M, Wester W, Sicard GA, Thompson R, Reilly JM. Indomethacin inhibits expansion of experimental aortic aneurysms via inhibition of the cox2 isoform of cyclooxygenase. J Vasc Surg 1999; 29: 884-92.
190. Walton LJ, Franklin IJ, Bayston T, et al. Inhibition of prostaglandin E2 synthesis in abdominal aortic aneurysms: implications for smooth muscle cell viability, inflammatory processes, and the expansion of abdominal aortic aneurysms. Circulation 1999; 100: 48-54.
191. Cipollone F, Fazia ML, Iezzi A, et al. Association between prostaglandin E receptor subtype EP4 overexpression and unstable phenotype in atherosclerotic plaques in human. Arterioscler Thromb Vasc Biol 2005; 25: 1925-31.
192. Pavlovic S, Du B, Sakamoto K, et al. Targeting prostaglandin E2 receptors as an alternative strategy to block cyclooxygenase-2-dependent extracellular matrix-induced matrix metalloproteinase-9 expression by macrophages. J Biol Chem 2006; 281: 3321-8.
193. Zucker S, Cao J, Chen WT. Critical appraisal of the use of matrix metalloproteinase inhibitors in cancer treatment. Oncogene 2000; 19: 6642-50.
194. Rouis M, Adamy C, Duverger N, et al. Adenovirus-mediated overexpression of tissue inhibitor of metalloproteinase-1 reduces atherosclerotic lesions in apolipoprotein E-deficient mice. Circulation 1999; 100: 533-40.
195. George SJ, Lloyd CT, Angelini GD, Newby AC, Baker AH. Inhibition of late vein graft neointima formation in human and porcine models by adenovirus-mediated overexpression of tissue inhibitor of metalloproteinase-3. Circulation 2000; 101: 296-304.
196. George SJ, Wan S, Hu J, MacDonald R, Johnson JL, Baker AH. Sustained reduction of vein graft neointima formation by ex vivo TIMP-3 gene therapy. Circulation 2011; 124: S135-42.
197. Forrester JS, Libby P. The inflammation hypothesis and its potential relevance to statin therapy. Am J Cardiol 2007; 99: 732-8.
198. Bellosta S, Via D, Canavesi M, et al. HMG-CoA reductase inhibitors reduce MMP-9 secretion by macrophages. Arterioscler Thromb Vasc Biol 1998; 18: 1671-8.
199. Aikawa M, Rabkin E, Okada Y, et al. Lipid lowering by diet reduces matrix metalloproteinase activity and increases collagen content of rabbit atheroma: a potential mechanism of lesion stabilization. Circulation 1998; 97: 2433-44.
200. Crisby M, Nordin-Fredriksson G, Shah PK, Yano J, Zhu J, Nilsson J. Pravastatin treatment increases collagen content and decreases lipid content, inflammation, metalloproteinases, and cell death in human carotid plaques: implications for plaque stabilization. Circulation 2001; 103: 926-33.
201. Luan Z, Chase AJ, Newby AC. Statins inhibit secretion of metalloproteinases-1,-2,-3, and-9 from vascular smooth muscle cells and macrophages. Arterioscler Thromb Vasc Biol 2003; 23: 769-75.
202. Fukumoto Y, Libby P, Rabkin E, et al. Statins alter smooth muscle cell accumulation and collagen content in established atheroma of watanabe heritable hyperlipidemic rabbits. Circulation 2001; 103: 993-9.
203. Scalia R, Gooszen ME, Jones SP, et al. Simvastatin exerts both anti-inflammatory and cardioprotective effects in apolipoprotein Edeficient mice. Circulation 2001; 103: 2598-603.
204. Jialal I, Stein D, Balis D, Grundy SM, Adams-Huet B, Devaraj S. Effect of hydroxymethyl glutaryl coenzyme a reductase inhibitor therapy on high sensitive C-reactive protein levels. Circulation 2001; 103: 1933-5.
205. Ridker PM, Rifai N, Lowenthal SP. Rapid reduction in C-reactive protein with cerivastatin among 785 patients with primary hypercholesterolemia. Circulation 2001; 103: 1191-3.
206. Devy L, Dransfield DT. New strategies for the next generation of matrix-metalloproteinase inhibitors: selectively targeting membrane-anchored MMPs with therapeutic antibodies. Biochem Res Int 2011; 2011: 191670.
207. Hu J, Van den Steen PE, Sang QX, Opdenakker G. Matrix metalloproteinase inhibitors as therapy for inflammatory and vascular diseases. Nat Rev Drug Discov 2007; 6: 480-98.
208. Rosenberg GA, Estrada EY, Mobashery S. Effect of synthetic matrix metalloproteinase inhibitors on lipopolysaccharide-induced blood-brain barrier opening in rodents: Differences in response based on strains and solvents. Brain Res 2007; 1133: 186-92.
209. Denis LJ, Verweij J. Matrix metalloproteinase inhibitors: present achievements and future prospects. Invest New Drugs 1997; 15: 175-85.
210. Parsons SL, Watson SA, Brown PD, Collins HM, Steele RJ. Matrix metalloproteinases. Br J Surg 1997; 84: 160-6.
211. Sood RR, Taheri S, Candelario-Jalil E, Estrada EY, Rosenberg GA. Early beneficial effect of matrix metalloproteinase inhibition on blood-brain barrier permeability as measured by magnetic resonance imaging countered by impaired long-term recovery after stroke in rat brain. J Cereb Blood Flow Metab 2008; 28: 431-8.
212. Nagel S, Heinemann PV, Heiland S, Koziol J, Gardner H, Wagner S. Selective MMP-inhibition with Ro 28-2653 in acute experimental stroke--a magnetic resonance imaging efficacy study. Brain Res 2011; 1368: 264-70.
213. Maquoi E, Sounni NE, Devy L, et al. Anti-invasive, antitumoral, and antiangiogenic efficacy of a pyrimidine-2,4,6-trione derivative, an orally active and selective matrix metalloproteinases inhibitor. Clin Cancer Res 2004; 10: 4038-47.
214. Shono T, Motoyama M, Tatsumi K, et al. A new synthetic matrix metalloproteinase inhibitor modulates both angiogenesis and urokinase type plasminogen activator activity. Angiogenesis 1998; 2: 319-29.
215. Wojtowicz-Praga S. Clinical potential of matrix metalloprotease inhibitors. Drugs R D 1999; 1: 117-29.
216. Quillard T, Tesmenitsky Y, Croce K, et al. Selective inhibition of matrix metalloproteinase-13 increases collagen content of established mouse atherosclerosis. Arterioscler Thromb Vasc Biol 2011; 31: 2464-72.
217. Franco C, Ho B, Mulholland D, et al. Doxycycline alters vascular smooth muscle cell adhesion, migration, and reorganization of fibrillar collagen matrices. Am J Pathol 2006; 168: 1697-709.
218. Sapadin AN, Fleischmajer R. Tetracyclines: nonantibiotic properties and their clinical implications. J Am Acad Dermatol 2006; 54: 258-65.
219. Axisa B, Loftus IM, Naylor AR, et al. Prospective, randomized, double-blind trial investigating the effect of doxycycline on matrix metalloproteinase expression within atherosclerotic carotid plaques. Stroke 2002; 33: 2858-64.
220. Brown DL, Desai KK, Vakili BA, Nouneh C, Lee HM, Golub LM. Clinical and biochemical results of the metalloproteinase inhibition with subantimicrobial doses of doxycycline to prevent acute coronary syndromes (MIDAS) pilot trial. Arterioscler Thromb Vasc Biol 2004; 24: 733-8.
221. Dodd BR, Spence RA. Doxycycline inhibition of abdominal aortic aneurysm growth: a systematic review of the literature. Curr Vasc Pharmacol 2011; 9: 471-8.
222. Golledge J, Norman PE. Current status of medical management for abdominal aortic aneurysm. 2011; 217: 57-63.
223. Bendeck MP, Conte M, Zhang M, Nili N, Strauss BH, Farwell SM. Doxycycline modulates smooth muscle cell growth, migration, and matrix remodeling after arterial injury. Am J Pathol 2002; 160: 1089-95.
224. Cowan KN, Jones PL, Rabinovitch M. Elastase and matrix metalloproteinase inhibitors induce regression, and tenascin-C antisense prevents progression, of vascular disease. J Clin Invest 2000; 105: 21-34.
225. Eriksson EE. Intravital microscopy on atherosclerosis in apolipoprotein e-deficient mice establishes microvessels as major entry pathways for leukocytes to advanced lesions. Circulation 2011; 124: 2129-38.
226. Forbes JM, Cooper ME. Mechanisms of diabetic complications. Physiol Rev 2013; 93: 137-88.
227. Chung AW, Hsiang YN, Matzke LA, McManus BM, van Breemen C, Okon EB. Reduced expression of vascular endothelial growth factor paralleled with the increased angiostatin expression resulting from the upregulated activities of matrix metalloproteinase-2 and-9 in human type 2 diabetic arterial vasculature. Circ Res 2006; 99: 140-8.
228. Hao F, Yu JD. High glucose enhance expression of matrix metalloproteinase-2 in smooth muscle cells. Acta Pharmacol Sin 2003; 24: 534-8.
229. Tarallo S, Beltramo E, Berrone E, Dentelli P, Porta M. Effects of high glucose and thiamine on the balance between matrix metalloproteinases and their tissue inhibitors in vascular cells. Acta Diabetol 2010; 47: 105-11.
230. Sun J, Xu Y, Dai Z, Sun Y. Intermittent high glucose enhances proliferation of vascular smooth muscle cells by upregulating osteopontin. Mol Cell Endocrinol 2009; 313: 64-9.
231. Uemura S, Matsushita H, Li W, et al. Diabetes mellitus enhances vascular matrix metalloproteinase activity: role of oxidative stress. Circ Res 2001; 88: 1291-8.
232. Worley JR, Hughes DA, Dozio N, Gavrilovic J, Sampson MJ. Low density lipoprotein from patients with Type 2 diabetes increases expression of monocyte matrix metalloproteinase and ADAM metalloproteinase genes. Cardiovasc Diabetol 2007; 6: 21.
233. Wilmer WA, Cosio FG. DNA binding of activator protein-1 is increased in human mesangial cells cultured in high glucose concentrations. Kidney Int 1998; 53: 1172-81.
234. Pascal MM, Knott RM, Forrester JV. Glucose mediated regulation of transforming growth factor beta in human retinal endothelial cells. Biochem Soc Trans 1996; 24: 228S.
235. Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature 2001; 414: 813-20.
236. Jormsjö S, Ye S, Moritz J, et al. Allele-specific regulation of matrix metalloproteinase-12 gene activity is associated with coronary artery luminal dimensions in diabetic patients with manifest coronary artery disease. Circ Res 2000; 86: 998-1003.
237. Yan SF, Ramasamy R, Naka Y, Schmidt AM. Glycation, inflammation, and RAGE: a scaffold for the macrovascular complications of diabetes and beyond. Circ Res 2003; 93: 1159-69.
238. Cipollone F, Iezzi A, Fazia M, et al. The receptor RAGE as a progression factor amplifying arachidonate-dependent inflammatory and proteolytic response in human atherosclerotic plaques: role of glycemic control. Circulation 2003; 108: 1070-7.
239. Jacob SS, Shastry P, Sudhakaran PR. Influence of nonenzymatically glycated collagen on monocyte-macrophage differentiation. Atherosclerosis 2001; 159: 333-41.
240. Federici M, Menghini R, Mauriello A, et al. Insulin-dependent activation of endothelial nitric oxide synthase is impaired by Olinked glycosylation modification of signaling proteins in human coronary endothelial cells. Circulation 2002; 106: 466-72.
241. Dandona P, Aljada A, Mohanty P, Ghanim H, Bandyopadhyay A, Chaudhuri A. Insulin suppresses plasma concentration of vascular endothelial growth factor and matrix metalloproteinase-9. Diabetes Care 2003; 26: 3310-4.
242. Sundström J, Evans JC, Benjamin EJ, et al. Relations of plasma matrix metalloproteinase-9 to clinical cardiovascular risk factors and echocardiographic left ventricular measures: the Framingham Heart Study. Circulation 2004; 109: 2850-6.
243. Marx N, Froehlich J, Siam L, et al. Antidiabetic PPAR gammaactivator rosiglitazone reduces MMP-9 serum levels in type 2 diabetic patients with coronary artery disease. Arterioscler Thromb Vasc Biol 2003; 23: 283-8.
244. Gonçalves FM, Jacob-Ferreira AL, Gomes VA, et al. Increased circulating levels of matrix metalloproteinase (MMP)-8, MMP-9, and pro-inflammatory markers in patients with metabolic syndrome. Clin Chim Acta 2009; 403: 173-7.
245. Signorelli SS, Malaponte G, Libra M. Plasma levels and zymographic activities of matrix metalloproteinases 2 and 9 in type II diabetics with peripheral arterial disease. Vasc Med 2005; 10: 1-6.
246. Derosa G, D'Angelo A, Scalise F. Comparison between metalloproteinases-2 and-9 in healthy subjects, diabetics, and subjects with acute coronary syndrome. Heart Vessels 2007; 22: 361-70.
247. Zayani Y, Allal-Elasmi M, Jacob MP, et al. Abnormal circulating levels of matrix metalloproteinases and their inhibitors in diabetes mellitus. Clin Lab 2012; 58: 779-85.
248. Baugh MD, Gavrilovic J, Davies IR, Hughes DA, Sampson MJ. Monocyte matrix metalloproteinase production in Type 2 diabetes and controls--a cross sectional study. Cardiovasc Diabetol 2003; 2: 3.
249. Portik-Dobos V, Anstadt MP, Hutchinson J, Bannan M, Ergul A. Evidence for a matrix metalloproteinase induction/activation system in arterial vasculature and decreased synthesis and activity in diabetes. Diabetes 2002; 51: 3063-8.
250. Das A, McGuire PG, Eriqat C, et al. Human diabetic neovascular membranes contain high levels of urokinase and metalloproteinase enzymes. Invest Ophthalmol Vis Sci 1999; 40: 809-13.
251. Salzmann J, Limb GA, Khaw PT, et al. Matrix metalloproteinases and their natural inhibitors in fibrovascular membranes of proliferative diabetic retinopathy. Br J Ophthalmol 2000; 84: 1091-6.
252. Lauhio A, Sorsa T, Srinivas R, et al. Urinary matrix metalloproteinase-8,-9,-14 and their regulators (TRY-1, TRY-2, TATI) in patients with diabetic nephropathy. Ann Med 2008; 40: 312-20.
253. Thrailkill KM, Clay Bunn R, Fowlkes JL. Matrix metalloproteinases: their potential role in the pathogenesis of diabetic nephropathy. Endocrine 2009; 35: 1-10.
254. Phillips AO, Steadman R, Morrisey K, Martin J, Eynstone L, Williams JD. Exposure of human renal proximal tubular cells to glucose leads to accumulation of type IV collagen and fibronectin by decreased degradation. Kidney Int 1997; 52: 973-84.
255. McLennan SV, Martell SK, Yue DK. Effects of mesangium glycation on matrix metalloproteinase activities: possible role in diabetic nephropathy. Diabetes 2002; 51: 2612-8.
256. Zhuang S, Kinsey GR, Rasbach K, Schnellmann RG. Heparinbinding epidermal growth factor and Src family kinases in proliferation of renal epithelial cells. Am J Physiol Renal Physiol 2008; 294: F459-68.
257. Haffner SM, Greenberg AS, Weston WM, Chen H, Williams K, Freed MI. Effect of rosiglitazone treatment on nontraditional markers of cardiovascular disease in patients with type 2 diabetes mellitus. Circulation 2002; 106: 679-84.
258. Goldstein BJ, Weissman PN, Wooddell MJ, Waterhouse BR, Cobitz AR. Reductions in biomarkers of cardiovascular risk in type 2 diabetes with rosiglitazone added to metformin compared with dose escalation of metformin: an EMPIRE trial sub-study. Curr Med Res Opin 2006; 22: 1715-23.
259. Lee CS, Kwon YW, Yang HM, et al. New mechanism of rosiglitazone to reduce neointimal hyperplasia: activation of glycogen synthase kinase-3beta followed by inhibition of MMP-9. Arterioscler Thromb Vasc Biol 2009; 29: 472-9.
260. Forst T, Karagiannis E, Lübben G, et al. Pleiotrophic and antiinflammatory effects of pioglitazone precede the metabolic activity in type 2 diabetic patients with coronary artery disease. Atherosclerosis 2008; 197: 311-7.
261. Game BA, Xu M, Lopes-Virella MF, Huang Y. Regulation of MMP-1 expression in vascular endothelial cells by insulin sensitizing thiazolidinediones. Atherosclerosis 2003; 169: 235-43.
262. Ruilope LM, Segura J. Losartan and other angiotensin II antagonists for nephropathy in type 2 diabetes mellitus: a review of the clinical trial evidence. Clin Ther 2003; 25: 3044-64.
263. Papadakis JA, Milionis HJ, Press M, Mikhailidis DP. Treating dyslipidaemia in non-insulin-dependent diabetes mellitus--a special reference to statins. J Diabetes Complications 2001; 15: 211-26.
264. Athyros VG, Papageorgiou AA, Symeonidis AN. Early benefit from structured care with atorvastatin in patients with coronary heart disease and diabetes mellitus. Angiology 2003; 54: 679-90.
265. Collins R, Armitage J, Parish S, Sleigh P, Peto R. MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial. Lancet 2003; 361: 2005-16.
266. Bellosta S, Ferri N, Arnaboldi L, Bernini F, Paoletti R, Corsini A. Pleiotropic effects of statins in atherosclerosis and diabetes. Diabetes Care 2000; 23: B72-8.
267. Luan Z, Chase AJ, Newby AC. Statins inhibit secretion of metalloproteinases-1,-2,-3, and-9 from vascular smooth muscle cells and macrophages. Arterioscler Thromb Vasc Biol 2003; 23: 769-75.
268. Song Y, Li C, Cai L. Fluvastatin prevents nephropathy likely through suppression of connective tissue growth factor-mediated extracellular matrix accumulation. Exp Mol Pathol 2004; 76: 66-75.
269. Furman C, Copin C, Kandoussi M. Rosuvastatin reduces MMP-7 secretion by human monocyte-derived macrophages: potential relevance to atherosclerotic plaque stability. Atherosclerosis 2004; 174: 93-8.
270. Balk EM, Lau J, Goudas LC. Effects of statins on nonlipid serum markers associated with cardiovascular disease: a systematic review. Ann Intern Med 2003; 139: 670-82.
271. Sager PT, Melani L, Lipka L. Effect of coadministration of ezetimibe and simvastatin on high-sensitivity C-reactive protein. Am J Cardiol 2003; 92: 1414-8.
272. Ridker PM, Rifai N, Clearfield M. Measurement of C-reactive protein for the targeting of statin therapy in the primary prevention of acute coronary events. N Engl J Med 2001; 344: 1959-65.
273. Elisaf M, Mikhailidis DP. Statins and renal function. Angiology 2002; 53: 493-502.
274. Daskalopoulou SS, Athyros VG, Elisaf M, Mikhailidis DP. Uric acid levels and vascular disease. Curr Med Res Opin 2004; 20: 951-4.
275. Athyros VG, Elisaf M, Papageorgiou AA. Effect of statins versus untreated dyslipidemia on serum uric acid levels in patients with coronary heart disease: a subgroup analysis of the GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) study. Am J Kidney Dis 2004; 43: 589-99.
276. Francis GA, Annicotte JS, Auwerx J. PPAR agonists in the treatment of atherosclerosis. Curr Opin Pharmacol 2003; 3: 186-91.
277. Marx N, Schönbeck U, Lazar MA, Libby P, Plutzky J. Peroxisome proliferator-activated receptor gamma activators inhibit gene expression and migration in human vascular smooth muscle cells. Circ Res 1998; 83: 1097-103.
278. Shu H, Wong B, Zhou G. Activation of PPARalpha or gamma reduces secretion of matrix metalloproteinase 9 but not interleukin 8 from human monocytic THP-1 cells. Biochem Biophys Res Commun 2000; 267: 345-9.
279. Rizos E, Bairaktari E, Ganotakis E, Tsimihodimos V, Mikhailidis DP, Elisaf M. Effect of ciprofibrate on lipoproteins, fibrinogen, renal function, and hepatic enzymes. J Cardiovasc Pharmacol Ther 2002; 7: 219-26.
280. Tsimihodimos V, Kostoula A, Kakafika A. Effect of fenofibrate on serum inflammatory markers in patients with high triglyceride values. J Cardiovasc Pharmacol Ther 2004; 9: 27-33.
281. Wierzbicki AS, Mikhailidis DP, Wray R. Statin-fibrate combination: therapy for hyperlipidemia: a review. Curr Med Res Opin 2003; 19: 155-68.
282. Kim YS, Joh TH. Microglia, major player in the brain inflammation: their roles in the pathogenesis of Parkinson's disease. Exp Mol Med 2006; 38: 333-47.
283. Block ML, Zecca L, Hong JS. Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Nat Rev Neurosci 2007; 8: 57-69.
284. Candelario-Jalil E, Yang Y, Rosenberg GA. Diverse roles of matrix metalloproteinases and tissue inhibitors of metalloproteinases in neuroinflammation and cerebral ischemia. Neuroscience 2009; 158: 983-94.
285. Rosenberg GA. Matrix metalloproteinases and their multiple roles in neurodegenerative diseases. Lancet Neurol 2009; 8: 205-16.
286. Yang Y, Hill JW, Rosenberg GA. Multiple roles of metalloproteinases in neurological disorders. Prog Mol Biol Transl Sci 2011; 99: 241-63.
287. Yang Y, Estrada EY, Thompson JF, Liu W, Rosenberg GA. Matrix metalloproteinase-mediated disruption of tight junction proteins in cerebral vessels is reversed by synthetic matrix metalloproteinase inhibitor in focal ischemia in rat. J Cereb Blood Flow Metab 2007; 27: 697-709.
288. Lo EH, Dalkara T, Moskowitz MA. Mechanisms, challenges and opportunities in stroke. Nat Rev Neurosci 2003; 4: 399-415.
289. Asahi M, Wang X, Mori T, et al. Effects of matrix metalloproteinase-9 gene knock-out on the proteolysis of blood-brain barrier and white matter components after cerebral ischemia. J Neurosci 2001; 21: 7724-32.
290. Gasche Y, Copin JC, Sugawara T, Fujimura M, Chan PH. Matrix metalloproteinase inhibition prevents oxidative stress-associated blood-brain barrier disruption after transient focal cerebral ischemia. J Cereb Blood Flow Metab 2001; 21: 1393-400.
291. Chang DI, Hosomi N, Lucero J, et al. Activation systems for latent matrix metalloproteinase-2 are upregulated immediately after focal cerebral ischemia. J Cereb Blood Flow Metab 2003; 23: 1408-19.
292. Liu W, Hendren J, Qin XJ, Shen J, Liu KJ. Normobaric hyperoxia attenuates early blood-brain barrier disruption by inhibiting MMP-9-mediated occludin degradation in focal cerebral ischemia. J Neurochem 2009; 108: 811-20.
293. Gurney KJ, Estrada EY, Rosenberg GA. Blood-brain barrier disruption by stromelysin-1 facilitates neutrophil infiltration in neuroinflammation. Neurobiol Dis 2006; 23: 87-96.
294. Asahi M, Asahi K, Jung JC, del Zoppo GJ, Fini ME, Lo EH. Role for matrix metalloproteinase 9 after focal cerebral ischemia: effects of gene knockout and enzyme inhibition with BB-94. J Cereb Blood Flow Metab 2000; 20: 1681-9.
295. Rosenberg GA, Estrada EY, Dencoff JE, Stetler-Stevenson WG. Tumor necrosis factor-alpha-induced gelatinase B causes delayed opening of the blood-brain barrier: an expanded therapeutic window. Brain Res 1995; 703: 151-5.
296. Candelario-Jalil E, Taheri S, Yang Y, et al. Cyclooxygenase inhibition limits blood-brain barrier disruption following intracerebral injection of tumor necrosis factor-alpha in the rat. J Pharmacol Exp Ther 2007; 323: 488-98.
297. Kauppinen TM, Swanson RA. Poly(ADP-ribose) polymerase-1 promotes microglial activation, proliferation, and matrix metalloproteinase-9-mediated neuron death. J Immunol 2005; 174: 2288-96.
298. del Zoppo GJ, Milner R, Mabuchi T, et al. Microglial activation and matrix protease generation during focal cerebral ischemia. Stroke 2007; 38: 646-51.
299. Wang L, Zhang ZG, Zhang RL, et al. Matrix metalloproteinase 2 (MMP2) and MMP9 secreted by erythropoietin-activated endothelial cells promote neural progenitor cell migration. J Neurosci 2006; 26: 5996-6003.
300. Lee SR, Kim HY, Rogowska J, et al. Involvement of matrix metalloproteinase in neuroblast cell migration from the subventricular zone after stroke. J Neurosci 2006; 26: 3491-5.
301. Harkness KA, Adamson P, Sussman JD, Davies-Jones GA, Greenwood J, Woodroofe MN. Dexamethasone regulation of matrix metalloproteinase expression in CNS vascular endothelium. Brain 2000; 123: 698-709.
302. Gottschall PE, Yu X. Cytokines regulate gelatinase A and B (matrix metalloproteinase 2 and 9) activity in cultured rat astrocytes. J Neurochem 1995; 64: 1513-20.
303. Lee WJ, Shin CY, Yoo BK, et al. Induction of matrix metalloproteinase-9 (MMP-9) in lipopolysaccharide-stimulated primary astrocytes is mediated by extracellular signal-regulated protein kinase 1/2 (Erk1/2). Glia 2003; 41: 15-24.
304. Hsieh HL, Yen MH, Jou MJ, Yang CM. Intracellular signalings underlying bradykinin-induced matrix metalloproteinase-9 expression in rat brain astrocyte-1. Cell Signal 2004; 16: 1163-76.
305. Wu CY, Hsieh HL, Jou MJ, Yang CM. Involvement of p42/p44 MAPK, p38 MAPK, JNK and nuclear factor-kappa B in interleukin-1beta-induced matrix metalloproteinase-9 expression in rat brain astrocytes. J Neurochem 2004; 90: 1477-88.
306. Woo CH, Lim JH, Kim JH. Lipopolysaccharide induces matrix metalloproteinase-9 expression via a mitochondrial reactive oxygen species-p38 kinase-activator protein-1 pathway in Raw 264.7 cells. J Immunol 2004; 173: 6973-80.
307. Rangaswami H, Bulbule A, Kundu GC. JNK1 differentially regulates osteopontin-induced nuclear factor-inducing kinase/MEKK1-dependent activating protein-1-mediated promatrix metalloproteinase-9 activation. J Biol Chem 2005; 280: 19381-92.
308. Han S, Ritzenthaler JD, Sitaraman SV, Roman J. Fibronectin increases matrix metalloproteinase 9 expression through activation of c-Fos via extracellular-regulated kinase and phosphatidylinositol 3-kinase pathways in human lung carcinoma cells. J Biol Chem 2006; 281: 29614-24.
309. Wang HH, Hsieh HL, Wu CY, Sun CC, Yang CM. Oxidized lowdensity lipoprotein induces matrix metalloproteinase-9 expression via a p42/p44 and JNK-dependent AP-1 pathway in brain astrocytes. Glia 2009; 57: 24-38.
310. Keller JN, Hanni KB, Markesbery WR. Oxidized low-density lipoprotein induces neuronal death: implications for calcium, reactive oxygen species, and caspases. J Neurochem 1999; 72: 2601-9.
311. Kim JA, Tran ND, Berliner JA, Fisher MJ. Minimally oxidized low-density lipoprotein regulates hemostasis factors of brain capillary endothelial cells. J Neurol Sci 2004; 217: 135-41.
312. Lupo G, Nicotra A, Giurdanella G, et al. Activation of phospholipase A(2) and MAP kinases by oxidized low-density lipoproteins in immortalized GP8.39 endothelial cells. Biochim Biophys Acta 2005; 1735: 135-50.
313. Vos CM, Sjulson L, Nath A, et al. Cytotoxicity by matrix metalloprotease-1 in organotypic spinal cord and dissociated neuronal cultures. Exp Neurol 2000; 163: 324-30.
314. Deb S, Gottschall PE. Increased production of matrix metalloproteinases in enriched astrocyte and mixed hippocampal cultures treated with beta-amyloid peptides. J Neurochem 1996; 66: 1641-7.
315. Rosenberg GA, Cunningham LA, Wallace J, et al. Immunohistochemistry of matrix metalloproteinases in reperfusion injury to rat brain: activation of MMP-9 linked to stromelysin-1 and microglia in cell cultures. Brain Res 2001; 893: 104-12.
316. Kim KS, Kim HY, Joe EH, Jou I. Matrix metalloproteinase-3 induction in rat brain astrocytes: focus on the role of two AP-1 elements. Biochem J 2008; 410: 605-11.
317. Crocker SJ, Milner R, Pham-Mitchell N, Campbell IL. Cell and agonist-specific regulation of genes for matrix metalloproteinases and their tissue inhibitors by primary glial cells. J Neurochem 2006; 98: 812-23.
318. Wells GM, Catlin G, Cossins JA, et al. Quantitation of matrix metalloproteinases in cultured rat astrocytes using the polymerase chain reaction with a multi-competitor cDNA standard. Glia 1996; 18: 332-40.
319. Anthony DC, Ferguson B, Matyzak MK, Miller KM, Esiri MM, Perry VH. Differential matrix metalloproteinase expression in cases of multiple sclerosis and stroke. Neuropathol Appl Neurobiol 1997; 23: 406-15.
320. Rosenberg GA, Sullivan N, Esiri MM. White matter damage is associated with matrix metalloproteinases in vascular dementia. Stroke 2001; 32: 1162-8.
321. Kim YS, Kim SS, Cho JJ, et al. Matrix metalloproteinase-3: a novel signaling proteinase from apoptotic neuronal cells that activates microglia. J Neurosci 2005; 25: 3701-11.
322. Kim YS, Choi DH, Block ML, et al. A pivotal role of matrix metalloproteinase-3 activity in dopaminergic neuronal degeneration via microglial activation. FASEB J 2007; 21: 179-87.
323. Woo MS, Park JS, Choi IY, Kim WK, Kim HS. Inhibition of MMP-3 or-9 suppresses lipopolysaccharide-induced expression of proinflammatory cytokines and iNOS in microglia. J Neurochem 2008; 106: 770-80.
324. Kim EM, Hwang O. Role of matrix metalloproteinase-3 in neurodegeneration. J Neurochem 2011; 116: 22-32.
325. Kim EM, Shin EJ, Choi JH, et al. Matrix metalloproteinase-3 is increased and participates in neuronal apoptotic signaling downstream of caspase-12 during endoplasmic reticulum stress. J Biol Chem 2010; 285: 16444-52.
326. Tan HK, Heywood D, Ralph GS, Bienemann A, Baker AH, Uney JB. Tissue inhibitor of metalloproteinase 1 inhibits excitotoxic cell death in neurons. Mol Cell Neurosci 2003; 22: 98-106.
327. Tejima E, Guo S, Murata Y, et al. Neuroprotective effects of overexpressing tissue inhibitor of metalloproteinase TIMP-1. J Neurotrauma 2009; 26: 1935-41.
328. Rosenberg GA. Inflammation and white matter damage in vascular cognitive impairment. Stroke 2009; 40: S20-3.
329. Semenza GL. Vasculogenesis, angiogenesis, and arteriogenesis: mechanisms of blood vessel formation and remodeling. J Cell Biochem 2007; 102: 840-7.
330. Nakaji K, Ihara M, Takahashi C, et al. Matrix metalloproteinase-2 plays a critical role in the pathogenesis of white matter lesions after chronic cerebral hypoperfusion in rodents. Stroke 2006; 37: 2816-23.
331. Chandler S, Coates R, Gearing A, Lury J, Wells G, Bone E. Matrix metalloproteinases degrade myelin basic protein. Neurosci Lett 1995; 201: 223-6.
332. Forsythe JA, Jiang BH, Iyer NV, et al. Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1. Mol Cell Biol 1996; 16: 4604-13.
333. Huang RQ, Cheng HL, Zhao XD, et al. Preliminary study on the effect of trauma-induced secondary cellular hypoxia in brain injury. Neurosci Lett 2010; 473: 22-7.
334. Ihara M, Tomimoto H, Kinoshita M, et al. Chronic cerebral hypoperfusion induces MMP-2 but not MMP-9 expression in the microglia and vascular endothelium of white matter. J Cereb Blood Flow Metab 2001; 21: 828-34.
335. Adair JC, Charlie J, Dencoff JE, et al. Measurement of gelatinase B (MMP-9) in the cerebrospinal fluid of patients with vascular dementia and Alzheimer disease. Stroke 2004; 35: e159-62.
336. Fernandez-Patron C, Radomski MW, Davidge ST. Vascular matrix metalloproteinase-2 cleaves big endothelin-1 yielding a novel vasoconstrictor. Circ Res 1999; 85: 906-11.
337. He S, Prasanna G, Yorio T. Endothelin-1-mediated signaling in the expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in astrocytes. Invest Ophthalmol Vis Sci 2007; 48: 3737-45.
338. Zhang WW, Badonic T, Höög A, et al. Structural and vasoactive factors influencing intracerebral arterioles in cases of vascular dementia and other cerebrovascular disease: a review. Immunohistochemical studies on expression of collagens, basal lamina components and endothelin-1. Dementia 1994; 5: 153-62.
339. Fritsch T, Smyth KA, Wallendal MS, Hyde T, Leo G, Geldmacher DS. Parkinson disease: research update and clinical management. South Med J 2012; 105: 650-6.
340. Sung JY, Park SM, Lee CH, et al. Proteolytic cleavage of extracellular secreted {alpha}-synuclein via matrix metalloproteinases. J Biol Chem 2005; 280: 25216-24.
341. McClain JA, Phillips LL, Fillmore HL. Increased MMP-3 and CTGF expression during lipopolysaccharide-induced dopaminergic neurodegeneration. Neurosci Lett 2009; 460: 27-31.
342. Choi DH, Kim EM, Son HJ, et al. A novel intracellular role of matrix metalloproteinase-3 during apoptosis of dopaminergic cells. J Neurochem 2008; 106: 405-15.
343. Levin J, Giese A, Boetzel K, et al. Increased alpha-synuclein aggregation following limited cleavage by certain matrix metalloproteinases. Exp Neurol 2009; 215: 201-8.
344. Kortekaas R, Leenders KL, van Oostrom JC, et al. Blood-brain barrier dysfunction in parkinsonian midbrain in vivo. Ann Neurol 2005; 57: 176-9.
345. Carvey PM, Zhao CH, Hendey B, et al. 6-Hydroxydopamineinduced alterations in blood-brain barrier permeability. Eur J Neurosci 2005; 22: 1158-68.
346. Zhao C, Ling Z, Newman MB, Bhatia A, Carvey PM. TNF-alpha knockout and minocycline treatment attenuates blood-brain barrier leakage in MPTP-treated mice. Neurobiol Dis 2007; 26: 36-46.
347. Ji KA, Eu MY, Kang SH, Gwag BJ, Jou I, Joe EH. Differential neutrophil infiltration contributes to regional differences in brain inflammation in the substantia nigra pars compacta and cortex. Glia 2008; 56: 1039-47.
348. Selkoe DJ. Alzheimer's disease: genes, proteins, and therapy. Physiol Rev 2001; 81: 741-66.
349. Honjo K, Black SE, Verhoeff NP. Alzheimer's disease, cerebrovascular disease, and the β-amyloid cascade. Can J Neurol Sci 2012; 39: 712-28.
350. Cavallucci V, D'Amelio M, Cecconi F. A toxicity in Alzheimer's disease. Mol Neurobio 2012; 45: 366-78.
351. LaFerla FM, Green KN, Oddo S. Intracellular amyloid-beta in Alzheimer's disease. Nat Rev Neurosci 2007; 8: 499-509.
352. Ahmad M, Takino T, Miyamori H, Yoshizaki T, Furukawa M, Sato H. Cleavage of amyloid-beta precursor protein (APP) by membrane-type matrix metalloproteinases. J Biochem 2006; 139: 517-26.
353. Allinson TM, Parkin ET, Turner AJ, Hooper NM. ADAMs family members as amyloid precursor protein alpha-secretases. J Neurosci Res 2003; 74: 342-52.
354. Endres K, Fahrenholz F. Upregulation of the alpha-secretase ADAM10--risk or reason for hope? FEBS J 2010; 277: 1585-96.
355. Saftig P, Reiss K. The "A Disintegrin And Metalloproteases" ADAM10 and ADAM17: novel drug targets with therapeutic potential? Eur J Cell Biol 2011; 90: 527-35.
356. Weskamp G, Cai H, Brodie TA, et al. Mice lacking the metalloprotease-disintegrin MDC9 (ADAM9) have no evident major abnormalities during development or adult life. Mol Cell Biol 2002; 22: 1537-44.
357. Cong L, Jia J. Promoter polymorphisms which regulate ADAM9 transcription are protective against sporadic Alzheimer's disease. Neurobiol Aging 2011; 32: 54-62.
358. Cissé MA, Sunyach C, Lefranc-Jullien S, Postina R, Vincent B, Checler F. The disintegrin ADAM9 indirectly contributes to the physiological processing of cellular prion by modulating ADAM10 activity. J Biol Chem 2005; 280: 40624-31.
359. Tousseyn T, Thathiah A, Jorissen E, et al. ADAM10, the ratelimiting protease of regulated intramembrane proteolysis of Notch and other proteins, is processed by ADAMS-9, ADAMS-15, and the gamma-secretase. J Biol Chem 2009; 284: 11738-47.
360. Parkin E, Harris B. A disintegrin and metalloproteinase (ADAM)-mediated ectodomain shedding of ADAM10. J Neurochem 2009; 108: 1464-79.
361. Postina R, Schroeder A, Dewachter I, et al. A disintegrinmetalloproteinase prevents amyloid plaque formation and hippocampal defects in an Alzheimer disease mouse model. J Clin Invest 2004; 113: 1456-64.
362. Schmitt U, Hiemke C, Fahrenholz F, Schroeder A. Over-expression of two different forms of the alpha-secretase ADAM10 affects learning and memory in mice. Behav Brain Res 2006; 175: 278-84.
363. Bell KF, Zheng L, Fahrenholz F, Cuello AC. ADAM-10 overexpression increases cortical synaptogenesis. Neurobiol Aging 2008; 29: 554-65.
364. Schroeder A, Fahrenholz F, Schmitt U. Effect of a dominantnegative form of ADAM10 in a mouse model of Alzheimer's disease. J Alzheimers Dis 2009; 16: 309-14.
365. Chen YY, Hehr CL, Atkinson-Leadbeater K, Hocking JC, McFarlane S. Targeting of retinal axons requires the metalloproteinase ADAM10. J Neurosci 2007; 27: 8448-56.
366. Jangouk P, Dehmel T, Meyer Zu Hörste G, Ludwig A, Lehmann HC, Kieseier BC. Involvement of ADAM10 in axonal outgrowth and myelination of the peripheral nerve. Glia 2009; 57: 1765-74.
367. Hattori M, Osterfield M, Flanagan JG. Regulated cleavage of a contact-mediated axon repellent. Science 2000; 289: 1360-5.
368. Janes PW, Saha N, Barton WA, et al. Adam meets Eph: an ADAM substrate recognition module acts as a molecular switch for ephrin cleavage in trans. Cell 2005; 123: 291-304.
369. Buxbaum JD, Liu KN, Luo Y, et al. Evidence that tumor necrosis factor alpha converting enzyme is involved in regulated alphasecretase cleavage of the Alzheimer amyloid protein precursor. J Biol Chem 1998; 273: 27765-7.
370. Merlos-Suárez A, Fernández-Larrea J, Reddy P, Baselga J, Arribas J. Pro-tumor necrosis factor-alpha processing activity is tightly controlled by a component that does not affect notch processing. J Biol Chem 1998; 273: 24955-62.
371. Slack BE, Ma LK, Seah CC. Constitutive shedding of the amyloid precursor protein ectodomain is up-regulated by tumour necrosis factor-alpha converting enzyme. Biochem J 2001; 357: 787-94.
372. Endres K, Anders A, Kojro E, Gilbert S, Fahrenholz F, Postina R. Tumor necrosis factor-alpha converting enzyme is processed by proprotein-convertases to its mature form which is degraded upon phorbol ester stimulation. Eur J Biochem 2003; 270: 2386-93.
373. Skovronsky DM, Fath S, Lee VM, Milla ME. Neuronal localization of the TNFalpha converting enzyme (TACE) in brain tissue and its correlation to amyloid plaques. J Neurobiol 2001; 49: 40-6.
374. Gottschall PE, Deb S. Regulation of matrix metalloproteinase expressions in astrocytes, microglia and neurons. Neuroimmunomodulation 1996; 3: 69-75.
375. Oh LY, Larsen PH, Krekoski CA, et al. Matrix metalloproteinase-9/gelatinase B is required for process outgrowth by oligodendrocytes. J Neurosci 1999; 19: 8464-75.
376. Leake A, Morris CM, Whateley J. Brain matrix metalloproteinase 1 levels are elevated in Alzheimer's disease. Neurosci Lett 2000; 291: 201-3.
377. Yin KJ, Cirrito JR, Yan P, et al. Matrix metalloproteinases expressed by astrocytes mediate extracellular amyloid-beta peptide catabolism. J Neurosci 2006; 26: 10939-48.
378. Walsh DM, Minogue AM, Sala Frigerio C, Fadeeva JV, Wasco W, Selkoe DJ. The APP family of proteins: similarities and differences. Biochem Soc Trans 2007; 35: 416-20.
379. Deb S, Gottschall PE. Increased production of matrix metalloproteinases in enriched astrocyte and mixed hippocampal cultures treated with beta-amyloid peptides. J Neurochem 1996; 66: 1641-7.
380. Yan P, Hu X, Song H, et al. Matrix metalloproteinase-9 degrades amyloid-beta fibrils in vitro and compact plaques in situ. J Biol Chem 2006; 281: 24566-74.
381. Ito S, Kimura K, Haneda M, Ishida Y, Sawada M, Isobe K. Induction of matrix metalloproteinases (MMPM3, MP12 and MMP13) expression in the microglia by amyloid-beta stimulation via the PI3K/Akt pathway. Exp Gerontol 2007; 42: 532-7.
382. Talamagas AA, Efthimiopoulos S, Tsilibary EC, Figueiredo-Pereira ME, Tzinia AK. Abeta(1-40)-induced secretion of matrix metalloproteinase-9 results in sAPPalpha release by association with cell surface APP. Neurobiol Dis 2007; 28: 304-15.
383. White AR, Du T, Laughton KM, et al. Degradation of the Alzheimer disease amyloid beta-peptide by metal-dependent upregulation of metalloprotease activity. J Biol Chem 2006; 281: 17670-80.
384. Caragounis A, Du T, Filiz G, et al. Differential modulation of Alzheimer's disease amyloid beta-peptide accumulation by diverse classes of metal ligands. Biochem J 2007; 407: 435-50.
385. Filiz G, Price KA, Caragounis A, Du T, Crouch PJ, White AR. The role of metals in modulating metalloprotease activity in the AD brain. Eur Biophys J 2008; 37: 315-21.
386. Selkoe DJ. Biochemistry and molecular biology of amyloid betaprotein and the mechanism of Alzheimer's disease. Handb Clin Neurol 2008; 89: 245-60.
387. Yoshiyama Y, Asahina M, Hattori T. Selective distribution of matrix metalloproteinase-3 (MMP-3) in Alzheimer's disease brain. Acta Neuropathol 2000; 99: 91-5.
388. Horstmann S, Budig L, Gardner H, et al. Matrix metalloproteinases in peripheral blood and cerebrospinal fluid in patients with Alzheimer's disease. Int Psychogeriatr 2010; 22: 966-72.
389. Stomrud E, Björkqvist M, Janciauskiene S, Minthon L, Hansson O. Alterations of matrix metalloproteinases in the healthy elderly with increased risk of prodromal Alzheimer's disease. Alzheimers Res Ther 2010; 2: 20.
390. Backstrom JR, Lim GP, Cullen MJ, Tökés ZA. Matrix metalloproteinase-9 (MMP-9) is synthesized in neurons of the human hippocampus and is capable of degrading the amyloid-beta peptide (1-40). J Neurosci 1996; 16: 7910-9.
391. Lorenzl S, Albers DS, Relkin N, et al. Increased plasma levels of matrix metalloproteinase-9 in patients with Alzheimer's disease. Neurochem Int 2003; 43: 191-6.
392. Brown PD. Synthetic inhibitors of matrix metalloproteinases. In: Parks WC, Mecham RP. Eds. Matrix metalloproteinases. San Diego, CA: Academic Press 1998; pp. 243-262.
393. Rosenberg GA, Kornfeld M, Estrada E, Kelley RO, Liotta LA, Stetler-Stevenson WG. TIMP-2 reduces proteolytic opening of blood-brain barrier by type IV collagenase. Brain Res 1992; 576: 203-7.
394. Gijbels K, Galardy RE, Steinman L. Reversal of experimental autoimmune encephalomyelitis with a hydroxamate inhibitor of matrix metalloproteases. J Clin Invest 1994; 94: 2177-82.
395. Hewson AK, Smith T, Leonard JP, Cuzner ML. Suppression of experimental allergic encephalomyelitis in the Lewis rat by the matrix metalloproteinase inhibitor Ro31-9790. Inflamm Res 1995; 44: 345-9.
396. Clements JM, Cossins JA, Wells GM, et al. Matrix metalloproteinase expression during experimental autoimmune encephalomyelitis and effects of a combined matrix metalloproteinase and tumour necrosis factor-alpha inhibitor. J Neuroimmunol 1997; 74: 85-94.
397. Mun-Bryce S, Rosenberg GA. Gelatinase B modulates selective opening of the blood-brain barrier during inflammation. Am J Physiol 1998; 274: R1203-11.
398. Sood RR, Taheri S, Candelario-Jalil E, Estrada EY, Rosenberg GA. Early beneficial effect of matrix metalloproteinase inhibition on blood-brain barrier permeability as measured by magnetic resonance imaging countered by impaired long-term recovery after stroke in rat brain. J Cereb Blood Flow Metab 2008; 28: 431-8.
399. Leib SL, Clements JM, Lindberg RL, et al. Inhibition of matrix metalloproteinases and tumour necrosis factor alpha converting enzyme as adjuvant therapy in pneumococcal meningitis. Brain 2001; 124: 1734-42.
400. Gu Z, Cui J, Brown S, et al. A highly specific inhibitor of matrix metalloproteinase-9 rescues laminin from proteolysis and neurons from apoptosis in transient focal cerebral ischemia. J Neurosci 2005; 25: 6401-8.
401. Lapchak PA, Chapman DF, Zivin JA. Metalloproteinase inhibition reduces thrombolytic (tissue plasminogen activator)-induced hemorrhage after thromboembolic stroke. Stroke 2000; 31: 3034-40.
402. Pfefferkorn T, Rosenberg GA. Closure of the blood-brain barrier by matrix metalloproteinase inhibition reduces rtPA-mediated mortality in cerebral ischemia with delayed reperfusion. Stroke 2003; 34: 2025-30.
403. Fisher JF, Mobashery S. Recent advances in MMP inhibitor design. Cancer Metastasis Rev 2006; 25: 115-36.
404. Puerta DT, Mongan J, Tran BL, McCammon JA, Cohen SM. Potent, selective pyrone-based inhibitors of stromelysin-1. J Am Chem Soc 2005; 127: 14148-9.
405. Corbitt CA, Lin J, Lindsey ML. Mechanisms to inhibit matrix metalloproteinase activity: where are we in the development of clinically relevant inhibitors? Recent Pat Anticancer Drug Discov 2007; 2: 135-42.
406. Coussens LM, Fingleton B, Matrisian LM. Matrix metalloproteinase inhibitors and cancer: trials and tribulations. Science 2002; 295: 2387-92.
407. Cho Y, Son HJ, Kim EM, et al. Doxycycline is neuroprotective against nigral dopaminergic degeneration by a dual mechanism involving MMP-3. Neurotox Res 2009; 16: 361-71.
408. Du Y, Ma Z, Lin S, et al. Minocycline prevents nigrostriatal dopaminergic neurodegeneration in the MPTP model of Parkinson's disease. Proc Natl Acad Sci USA 2001; 98: 14669-74.
409. Tikka T, Fiebich BL, Goldsteins G, Keinanen R, Koistinaho J. Minocycline, a tetracycline derivative, is neuroprotective against excitotoxicity by inhibiting activation and proliferation of microglia. J Neurosci 2001; 21: 2580-8.
410. Wu DC, Jackson-Lewis V, Vila M, et al. Blockade of microglial activation is neuroprotective in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson disease. J Neurosci 2002; 22: 1763-71.
411. Matsukawa N, Yasuhara T, Hara K, et al. Therapeutic targets and limits of minocycline neuroprotection in experimental ischemic stroke. BMC Neurosci 2009; 10: 126.
412. Moon M, Kim HG, Hwang L, et al. Neuroprotective effect of ghrelin in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease by blocking microglial activation. Neurotox Res 2009; 15: 332-47.
413. Lee J, Lim E, Kim Y, Li E, Park S. Ghrelin attenuates kainic acidinduced neuronal cell death in the mouse hippocampus. J Endocrinol 2010; 205: 263-70.
414. Lee EJ, Kim SY, Hyun JW, Min SW, Kim DH, Kim HS. Glycitein inhibits glioma cell invasion through down-regulation of MMP-3 and MMP-9 gene expression. Chem Biol Interact 2010; 185: 18-24.
415. Kim S, Moon M, Park S. Exendin-4 protects dopaminergic neurons by inhibition of microglial activation and matrix metalloproteinase-3 expression in an animal model of Parkinson's disease. J Endocrinol 2009; 202: 431-9.
416. Kojro E, Gimpl G, Lammich S, Marz W, Fahrenholz F. Low cholesterol stimulates the nonamyloidogenic pathway by its effect on the alpha-secretase ADAM 10. Proc Natl Acad Sci USA 2001; 98: 5815-20.
417. Matthews V, Schuster B, Schütze S, et al. Cellular cholesterol depletion triggers shedding of the human interleukin-6 receptor by ADAM10 and ADAM17 (TACE). J Biol Chem 2003; 278: 38829-39.
418. Felson DT. Developments in the clinical understanding of osteoarthritis. Arthritis Res Ther 2009; 11: 203.
419. Goldring MB, Goldring SR. Articular cartilage and subchondral bone in the pathogenesis of osteoarthritis. Ann NY Acad Sci 2010; 1192: 230-7.
420. Blom AB, van Lent PL, Holthuysen AE, et al. Synovial lining macrophages mediate osteophyte formation during experimental osteoarthritis. Osteoarthritis Cartilage 2004; 12: 627-35.
421. Goldring MB, Goldring SR. Osteoarthritis. J Cell Physiol 2007; 213: 626-34.
422. Heinegård D, Saxne T. The role of the cartilage matrix in osteoarthritis. Nat Rev Rheumatol 2011; 7: 50-6.
423. Nagase H, Kashiwagi M. Aggrecanases and cartilage matrix degradation. Arthritis Res Ther 2003; 5: 94-103.
424. Billinghurst RC, Dahlberg L, Ionescu M, et al. Enhanced cleavage of type II collagen by collagenases in osteoarthritic articular cartilage. J Clin Invest 1997; 99: 1534-45.
425. Lohmander LS, Atley LM, Pietka TA, Eyre DR. The release of crosslinked peptides from type II collagen into human synovial fluid is increased soon after joint injury and in osteoarthritis. Arthritis Rheum 2003; 48: 3130-9.
426. Lee JH, Fitzgerald JB, Dimicco MA, Grodzinsky AJ. Mechanical injury of cartilage explants causes specific time-dependent changes in chondrocyte gene expression. Arthritis Rheum 2005; 52: 2386-95.
427. Guo D, Tan W, Wang F, et al. Proteomic analysis of human articular cartilage: identification of differentially expressed proteins in knee osteoarthritis. Joint Bone Spine 2008; 75: 439-44.
428. Kuno K, Okada Y, Kawashima H, et al. ADAMTS-1 cleaves a cartilage proteoglycan, aggrecan. FEBS Lett 2000; 478: 241-5.
429. Somerville RP, Longpre JM, Jungers KA, et al. Characterization of ADAMTS-9 and ADAMTS-20 as a distinct ADAMTS subfamily related to Caenorhabditis elegans GON-1. J Biol Chem 2003; 278: 9503-13.
430. Collins-Racie LA, Flannery CR, Zeng W, et al. ADAMTS-8 exhibits aggrecanase activity and is expressed in human articular cartilage. Matrix Biol 2004; 23: 219-30.
431. Zeng W, Corcoran C, Collins-Racie LA, Lavallie ER, Morris EA, Flannery CR. Glycosaminoglycan-binding properties and aggrecanase activities of truncated ADAMTSs: comparative analyses with ADAMTS-5,-9,-16 and-18. Biochim Biophys Acta 2006; 1760: 517-24.
432. Gendron C, Kashiwagi M, Lim NH, et al. Proteolytic activities of human ADAMTS-5: comparative studies with ADAMTS-4. J Biol Chem 2007; 282: 18294-306.
433. Sandy JD, Verscharen C. Analysis of aggrecan in human knee cartilage and synovial fluid indicates that aggrecanase (ADAMTS) activity is responsible for the catabolic turnover and loss of whole aggrecan whereas other protease activity is required for C-terminal processing in vivo. Biochem J 2001; 358: 615-26.
434. Sandy JD. A contentious issue finds some clarity: on the independent and complementary roles of aggrecanase activity and MMP activity in human joint aggrecanolysis. Osteoarthritis Cartilage 2006; 14: 95-100.
435. Little CB, Meeker CT, Golub SB, et al. Blocking aggrecanase cleavage in the aggrecan interglobular domain abrogates cartilage erosion and promotes cartilage repair. J Clin Invest 2007; 117: 1627-36.
436. Bau B, Gebhard PM, Haag J, Knorr T, Bartnik E, Aigner T. Relative messenger RNA expression profiling of collagenases and aggrecanases in human articular chondrocytes in vivo and in vitro. Arthritis Rheum 2002; 46: 2648-57.
437. Bondeson J, Wainwright SD, Lauder S, Amos N, Hughes CE. The role of synovial macrophages and macrophage-produced cytokines in driving aggrecanases, matrix metalloproteinases, and other destructive and inflammatory responses in osteoarthritis. Arthritis Res Ther 2006; 8: R187.
438. Glasson SS, Askew R, Sheppard B, et al. Deletion of active ADAMTS5 prevents cartilage degradation in a murine model of osteoarthritis. Nature 2005; 434: 644-8.
439. Stanton H, Rogerson FM, East CJ, et al. ADAMTS5 is the major aggrecanase in mouse cartilage in vivo and in vitro. Nature 2005; 434: 648-52.
440. Glasson SS, Askew R, Sheppard B et al. Characterization of and osteoarthritis susceptibility in ADAMTS-4-knockout mice. Arthritis Rheum 2004; 50: 2547-58.
441. Song RH, Tortorella MD, Malfait AM et al. Aggrecan degradation in human articular cartilage explants is mediated by both ADAMTS-4 and ADAMTS-5. Arthritis Rheum 2007; 56: 575-85.
442. Naito S, Shiomi T, Okada A, et al. Expression of ADAMTS4 (aggrecanase-1) in human osteoarthritic cartilage. Pathol Int 2007; 57: 703-11.
443. Pratta MA, Scherle PA, Yang G, Liu RQ, Newton RC. Induction of aggrecanase 1 (ADAM-TS4) by interleukin-1 occurs through activation of constitutively produced protein. Arthritis Rheum 2003; 48: 119-33.
444. Rogerson FM, Stanton H, East CJ, et al. Evidence of a novel aggrecan-degrading activity in cartilage: Studies of mice deficient in both ADAMTS-4 and ADAMTS-5. Arthritis Rheum 2008; 58: 1664-73.
445. Mitchell PG, Magna HA, Reeves LM, et al. Cloning, expression, and type II collagenolytic activity of matrix metalloproteinase-13 from human osteoarthritic cartilage. J Clin Invest 1996; 97: 761-8.
446. Kevorkian L, Young DA, Darrah C, et al. Expression profiling of metalloproteinases and their inhibitors in cartilage. Arthritis Rheum 2004; 50: 131-41.
447. Little CB, Barai A, Burkhardt D, et al. Matrix metalloproteinase 13-deficient mice are resistant to osteoarthritic cartilage erosion but not chondrocyte hypertrophy or osteophyte development. Arthritis Rheum 2009; 60: 3723-33.
448. Inada M, Wang Y, Byrne MH, et al. Critical roles for collagenase-3 (Mmp13) in development of growth plate cartilage and in endochondral ossification. Proc Natl Acad Sci USA 2004; 101: 17192-7.
449. Stickens D, Behonick DJ, Ortega N, et al. Altered endochondral bone development in matrix metalloproteinase 13-deficient mice. Development 2004; 131: 5883-95.
450. Zack MD, Malfait AM, Skepner AP, et al. ADAM-8 isolated from human osteoarthritic chondrocytes cleaves fibronectin at Ala(271). Arthritis Rheum 2009; 60: 2704-13.
451. van Meurs J, van Lent P, Stoop R, et al. Cleavage of aggrecan at the Asn341-Phe342 site coincides with the initiation of collagen damage in murine antigen-induced arthritis: a pivotal role for stromelysin 1 in matrix metalloproteinase activity. Arthritis Rheum 1999; 42: 2074-84.
452. Kubota E, Imamura H, Kubota T, Shibata T, Murakami K. Interleukin 1 beta and stromelysin (MMP3) activity of synovial fluid as possible markers of osteoarthritis in the temporomandibular joint. J Oral Maxillofac Surg 1997; 55: 20-7.
453. Garner BC, Stoker AM, Kuroki K, Evans R, Cook CR, Cook JL. Using animal models in osteoarthritis biomarker research. J Knee Surg 2011; 24: 251-64.
454. Tetlow LC, Adlam DJ, Woolley DE. Matrix metalloproteinase and proinflammatory cytokine production by chondrocytes of human osteoarthritic cartilage: associations with degenerative changes. Arthritis Rheum 2001; 44: 585-94.
455. Sofat N. Analysing the role of endogenous matrix molecules in the development of osteoarthritis. Int J Exp Pathol 2009; 90: 463-79.
456. Klatt AR, Paul-Klausch B, Klinger G, et al. A critical role for collagen II in cartilage matrix degradation: collagen II induces proinflammatory cytokines and MMPs in primary human chondrocytes. J Orthop Res 2009; 27: 65-70.
457. Fichter M, Körner U, Schömburg J, Jennings L, Cole AA, Mollenhauer J. Collagen degradation products modulate matrix metalloproteinase expression in cultured articular chondrocytes. J Orthop Res 2006; 24: 63-70.
458. Jennings L, Wu L, King KB, Hämmerle H, Cs-Szabo G, Mollenhauer J. The effects of collagen fragments on the extracellular matrix metabolism of bovine and human chondrocytes. Connect Tissue Res 2001; 42: 71-86.
459. Pelletier JP, Martel-Pelletier J, Abramson SB. Osteoarthritis, an inflammatory disease: potential implication for the selection of new therapeutic targets. Arthritis Rheum 2001; 44: 1237-47.
460. Benito MJ, Veale DJ, FitzGerald O, van den Berg WB, Bresnihan B. Synovial tissue inflammation in early and late osteoarthritis. Ann Rheum Dis 2005; 64: 1263-7.
461. Goldring MB, Otero M, Tsuchimochi K, Ijiri K, Li Y. Defining the roles of inflammatory and anabolic cytokines in cartilage metabolism. Ann Rheum Dis 2008; 67: 75-82.
462. Heinegård D, Saxne T. The role of the cartilage matrix in osteoarthritis. Nat Rev Rheumatol 2011; 7: 50-6.
463. Kapoor M, Martel-Pelletier J, Lajeunesse D, Pelletier JP, Fahmi H. Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nat Rev Rheumatol 2011; 7: 33-42.
464. Haynes MK, Hume EL, Smith JB. Phenotypic characterization of inflammatory cells from osteoarthritic synovium and synovial fluids. Clin Immunol 2002; 105: 315-25.
465. Sawaji Y, Hynes J, Vincent T, Saklatvala J. Fibroblast growth factor 2 inhibits induction of aggrecanase activity in human articular cartilage. Arthritis Rheum 2008; 58: 3498-509.
466. Tortorella MD, Malfait AM, Deccico C, Arner E. The role of ADAM-TS4 (aggrecanase-1) and ADAM-TS5 (aggrecanase-2) in a model of cartilage degradation. Osteoarthritis Cartilage 2001; 9: 539-52.
467. Yamanishi Y, Boyle DL, Clark M, et al. Expression and regulation of aggrecanase in arthritis: the role of TGF-beta. J Immunol 2002; 168: 1405-12.
468. Koshy PJ, Lundy CJ, Rowan AD, et al. The modulation of matrix metalloproteinase and ADAM gene expression in human chondrocytes by interleukin-1 and oncostatin M: a time-course study using real-time quantitative reverse transcription-polymerase chain reaction. Arthritis Rheum 2002; 46: 961-7.
469. Zwerina J, Redlich K, Polzer K, et al. TNF-induced structural joint damage is mediated by IL-1. Proc Natl Acad Sci USA 2007; 104: 11742-7.
470. Séguin CA, Bojarski M, Pilliar RM, Roughley PJ, Kandel RA. Differential regulation of matrix degrading enzymes in a TNFalpha-induced model of nucleus pulposus tissue degeneration. Matrix Biol 2006; 25: 409-18.
471. Kobayashi M, Squires GR, Mousa A, et al. Role of interleukin-1 and tumor necrosis factor alpha in matrix degradation of human osteoarthritic cartilage. Arthritis Rheum 2005; 52: 128-35.
472. Page Thomas DP, King B, Stephens T, Dingle JT. In vivo studies of cartilage regeneration after damage induced by catabolin/interleukin-1. Ann Rheum Dis 1991; 50: 75-80.
473. Barksby HE, Hui W, Wappler I, et al. Interleukin-1 in combination with oncostatin M up-regulates multiple genes in chondrocytes: implications for cartilage destruction and repair. Arthritis Rheum 2006; 54: 540-50.
474. Vuolteenaho K, Moilanen T, Jalonen U, et al. TGFbeta inhibits IL-1-induced iNOS expression and NO production in immortalized chondrocytes. Inflamm Res 2005; 54: 420-7.
475. Glasson SS. In vivo osteoarthritis target validation utilizing genetically-modified mice. Curr Drug Targets 2007; 8: 367-76.
476. Van den Berg WB. Lessons from animal models of arthritis. Curr Rheumatol Rep 2002; 4: 232-9.
477. van der Kraan PM, Blaney Davidson EN, van den Berg WB. A role for age-related changes in TGFbeta signaling in aberrant chondrocyte differentiation and osteoarthritis. Arthritis Res Ther 2010; 12: 201.
478. Blaney Davidson EN, Remst DF, Vitters EL, et al. Increase in ALK1/ALK5 ratio as a cause for elevated MMP-13 expression in osteoarthritis in humans and mice. J Immunol 2009; 182: 7937-45.
479. Hoff P, Buttgereit F, Burmester GR, et al. Osteoarthritis synovial fluid activates pro-inflammatory cytokines in primary human chondrocytes. Int Orthop 2013; 37: 145-51.
480. Pulai JI, Chen H, Im HJ, et al. NF-kappa B mediates the stimulation of cytokine and chemokine expression by human articular chondrocytes in response to fibronectin fragments. J Immunol 2005; 174: 5781-8.
481. Appleton CT, Pitelka V, Henry J, Beier F. Global analyses of gene expression in early experimental osteoarthritis. Arthritis Rheum 2007; 56: 1854-68.
482. Brühl H, Mack M, Niedermeier M, Lochbaum D, Schölmerich J, Straub RH. Functional expression of the chemokine receptor CCR7 on fibroblast-like synoviocytes. Rheumatology (Oxford) 2008; 47: 1771-4.
483. Brew K, Nagase H. The tissue inhibitors of metalloproteinases (TIMPs): an ancient family with structural and functional diversity. Biochim Biophys Acta 2010; 1803: 55-71.
484. Hashimoto G, Aoki T, Nakamura H, Tanzawa K, Okada Y. Inhibition of ADAMTS4 (aggrecanase-1) by tissue inhibitors of metalloproteinases (TIMP-1, 2, 3 and 4). FEBS Lett 2001; 494: 192-5.
485. Kashiwagi M, Tortorella M, Nagase H, Brew K. TIMP-3 is a potent inhibitor of aggrecanase 1 (ADAM-TS4) and aggrecanase 2 (ADAM-TS5). J Biol Chem 2010; 276: 12501-4.
486. Wayne GJ, Deng SJ, Amour A, et al. TIMP-3 inhibition of ADAMTS-4 (Aggrecanase-1) is modulated by interactions between aggrecan and the C-terminal domain of ADAMTS-4. J Biol Chem 2007; 282: 20991-8.
487. Gendron C, Kashiwagi M, Hughes C, Caterson B, Nagase H. TIMP-3 inhibits aggrecanase-mediated glycosaminoglycan release from cartilage explants stimulated by catabolic factors. FEBS Lett 2003; 555: 431-6.
488. Sahebjam S, Khokha R, Mort JS. Increased collagen and aggrecan degradation with age in the joints of Timp3(-/-) mice. Arthritis Rheum 2007; 56: 905-9.
489. Mahmoodi M, Sahebjam S, Smookler D, Khokha R, Mort JS. Lack of tissue inhibitor of metalloproteinases-3 results in an enhanced inflammatory response in antigen-induced arthritis. Am J Pathol 2005; 166: 1733-40.
490. Morris KJ, Cs-Szabo G, Cole AA. Characterization of TIMP-3 in human articular talar cartilage. Connect Tissue Res 2010; 51: 478-90.
491. Burrage PS, Brinckerhoff CE. Molecular targets in osteoarthritis: metalloproteinases and their inhibitors. Curr Drug Targets 2007; 8: 293-303.
492. Yao W, Wasserman ZR, Chao M, et al. Design and synthesis of a series of (2R)-N(4)-hydroxy-2-(3-hydroxybenzyl)-N(1)-[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]butanediamide derivatives as potent, selective, and orally bioavailable aggrecanase inhibitors. J Med Chem 2001; 44: 3347-50.
493. Cherney RJ, Mo R, Meyer DT, et al. Potent and selective aggrecanase inhibitors containing cyclic P1 substituents. Bioorg Med Chem Lett 2003; 13: 1297-300.
494. Gilbert AM, Bursavich MG, Lombardi S, et al. 5-(1H-pyrazol-4-yl)methylene)-2-thioxothiazolidin-4-one inhibitors of ADAMTS-5. Bioorg Med Chem Lett 2007; 17: 1189-92.
495. Bursavich MG, Gilbert AM, Lombardi S, et al. Synthesis and evaluation of aryl thioxothiazolidinone inhibitors of ADAMTS-5 (Aggrecanase-2). Bioorg Med Chem Lett 2007; 17: 1185-8.
496. Glaser KB, Li J, Aakre ME, et al. Transforming growth factor beta mimetics: discovery of 7-[4-(4-cyanophenyl)phenoxy]-heptanohydroxamic acid, a biaryl hydroxamate inhibitor of histone deacetylase. Mol Cancer Ther 2002; 1: 759-68.
497. Zhang H, Zou K, Tesseur I, Wyss-Coray T. Small molecule tgfbeta mimetics as potential neuroprotective factors. Curr Alzheimer Res 2005; 2: 183-6.
498. Bernard DJ, Lee KB, Santos MM. Activin B can signal through both ALK4 and ALK7 in gonadotrope cells. Reprod Biol Endocrinol 2006; 4: 52.
499. Bondeson J, Lauder S, Wainwright S, et al. Adenoviral gene transfer of the endogenous inhibitor IkappaBalpha into human osteoarthritis synovial fibroblasts demonstrates that several matrix metalloproteinases and aggrecanases are nuclear factor-kappaBdependent. J Rheumatol 2007; 343: 523-33.
500. Bondeson J, Wainwright S, Hughes C, Caterson B. The regulation of the ADAMTS4 and ADAMTS5 aggrecanases in osteoarthritis: a review. Clin Exp Rheumatol 2008; 26: 139-45.
501. Pattoli MA, MacMaster JF, Gregor KR, Burke JR. Collagen and aggrecan degradation is blocked in interleukin-1-treated cartilage explants by an inhibitor of IkappaB kinase through suppression of metalloproteinase expression. J Pharmacol Exp Ther 2005; 315: 382-8.
502. Pelletier JP, Martel-Pelletier J, Raynauld JP. Most recent developments in strategies to reduce the progression of structural changes in osteoarthritis: today and tomorrow. Arthritis Res Ther 2006; 8: 206.