Cysteine protease cathepsins in atherosclerosis-based vascular disease and its complications

Hypertension

Volumn 58, Issue 6, 2011, Pages 978-986

  Cheng, Xian Wu ^a,b,c   Huang, Zhe ^a   Kuzuya, Masafumi ^a   Okumura, Kenji ^a   Murohara, Toyoaki ^a  

^a NAGOYA UNIVERSITY GRADUATE SCHOOL OF MEDICINE   (Japan)

^b YANBIAN UNIVERSITY   (China)

^c Kyung Hee University College of Medicine   (South Korea)

Author keywords

Cell events; Cystatin C; Cysteinyl cathepsins; Extracellular matrix degradation; Vascular disease

Indexed keywords

CATHEPSIN; CATHEPSIN B; CATHEPSIN K; CATHEPSIN L; CATHEPSIN S; DIPEPTIDYL PEPTIDASE I; HLA ANTIGEN CLASS 2;

ABDOMINAL AORTA ANEURYSM; ACIDIFICATION; ANTIGEN PRESENTATION; APOPTOSIS; ATHEROSCLEROSIS; ATHEROSCLEROSIS BASED VASCULAR DISEASE; CALCIFICATION; CD25+ T LYMPHOCYTE; CD4+ T LYMPHOCYTE; CELL ADHESION; CELL MIGRATION; CELL PROLIFERATION; CYTOKINE RESPONSE; ENZYME ACTIVITY; ENZYME METABOLISM; ENZYME REGULATION; EXTRACELLULAR MATRIX; GOLGI COMPLEX; HUMAN; LIPID METABOLISM; LIPID TRANSPORT; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN PROCESSING; PROTEIN SYNTHESIS; RESTENOSIS; REVIEW; THROMBOSIS; VASA VASORUM; VASCULAR DISEASE;

ANEURYSM; ANIMALS; ANTIGEN PRESENTATION; APOPTOSIS; ATHEROSCLEROSIS; BIOLOGICAL MARKERS; CALCINOSIS; CATHEPSINS; CELL ADHESION; CHEMOTAXIS, LEUKOCYTE; CHOLESTEROL; CYSTEINE PROTEASES; CYTOKINES; ENDOSOMES; ENDOTHELIUM, VASCULAR; EXTRACELLULAR MATRIX; EXTRACELLULAR MATRIX PROTEINS; FOAM CELLS; HUMANS; LIPOPROTEINS; LYSOSOMES; THROMBOSIS; VASA VASORUM; VASCULITIS;

EID: 83155181503     PISSN: 0194911X     EISSN: 15244563     Source Type: Journal    
DOI: 10.1161/HYPERTENSIONAHA.111.180935     Document Type: Review

References (98)

1. Kuzuya M, Kanda S, Sasaki T, Tamaya-Mori N, Cheng XW, Itoh T, Itohara S, Iguchi A. Deficiency of gelatinase a suppresses smooth muscle cell invasion and development of experimental intimal hyperplasia. Circulation. 2003;108:1375-1381.
2. 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;26:1120-1125.
3. Peterson JT, Hallak H, Johnson L, Li H, O'Brien PM, Sliskovic DR, Bocan TM, Coker ML, Etoh T, Spinale FG. Matrix metalloproteinase inhibition attenuates left ventricular remodeling and dysfunction in a rat model of progressive heart failure. Circulation. 2001;103:2303-2309.
4. Carmeliet P, Moons L, Lijnen R, Baes M, Lemaitre V, Tipping P, Drew A, Eeckhout Y, Shapiro S, Lupu F, Collen D. Urokinase-generated plasmin activates matrix metalloproteinases during aneurysm formation. Nat Genet. 1997;17:439-444.
5. Turk V, Turk B, Guncar G, Turk D, Kos J. Lysosomal cathepsins: structure, role in antigen processing and presentation, and cancer. Adv Enzyme Regul. 2002;42:285-303.
6. Turk V, Turk B, Turk D. Lysosomal cysteine proteases: facts and opportunities. EMBO J. 2001;20:4629-4633.
7. Funkelstein L, Toneff T, Mosier C, Hwang SR, Beuschlein F, Lichtenauer UD, Reinheckel T, Peters C, Hook V. Major role of cathepsin L for producing the peptide hormones ACTH, β-endorphin, and α-MSH, illustrated by protease gene knockout and expression. J Biol Chem. 2008;283:35652-35659.
8. Friedrichs B, Tepel C, Reinheckel T, Deussing J, von Figura K, Herzog V, Peters C, Saftig P, Brix K. Thyroid functions of mouse cathepsins B, K, and L. J Clin Invest. 2003;111:1733-1745.
9. Sukhova GK, Shi GP, Simon DI, Chapman HA, Libby P. Expression of the elastolytic cathepsins S and K in human atheroma and regulation of their production in smooth muscle cells. J Clin Invest. 1998;102:576-583.
10. Cheng XW, Obata K, Kuzuya M, Izawa H, Nakamura K, Asai E, Nagasaka T, Saka M, Kimata T, Noda A, Nagata K, Jin H, Shi GP, Iguchi A, Murohara T, Yokota M. Elastolytic cathepsin induction/activation system exists in myocardium and is upregulated in hypertensive heart failure. Hypertension. 2006;48:979-987.
11. Cheng XW, Murohara T, Kuzuya M, Izawa H, Sasaki T, Obata K, Nagata K, Nishizawa T, Kobayashi M, Yamada T, Kim W, Sato K, Shi GP, Okumura K, Yokota M. Superoxide-dependent cathepsin activation is associated with hypertensive myocardial remodeling and represents a target for angiotensin II type 1 receptor blocker treatment. Am J Pathol. 2008;173:358-369.
12. Cheng XW, Kuzuya M, Sasaki T, Arakawa K, Kanda S, Sumi D, Koike T, Maeda K, Tamaya-Mori N, Shi GP, Saito N, Iguchi A. Increased expression of elastolytic cysteine proteases, cathepsins S and K, in the neointima of balloon-injured rat carotid arteries. Am J Pathol. 2004;164:243-251.
13. Sukhova GK, Zhang Y, Pan JH, Wada Y, Yamamoto T, Naito M, Kodama T, Tsimikas S, Witztum JL, Lu ML, Sakara Y, Chin MT, Libby P, Shi GP. Deficiency of cathepsin S reduces atherosclerosis in LDL receptor-deficient mice. J Clin Invest. 2003;111:897-906.
14. Liu J, Ma L, Yang J, Ren A, Sun Z, Yan G, Sun J, Fu H, Xu W, Hu C, Shi GP. Increased serum cathepsin S in patients with atherosclerosis and diabetes. Atherosclerosis. 2006;186:411-419.
15. Liu J, Sukhova GK, Yang JT, Sun J, Ma L, Ren A, Xu WH, Fu H, Dolganov GM, Hu C, Libby P, Shi GP. Cathepsin L expression and regulation in human abdominal aortic aneurysm, atherosclerosis, and vascular cells. Atherosclerosis. 2006;184:302-311.
16. Mohamed MM, Sloane BF. Cysteine cathepsins: multifunctional enzymes in cancer. Nat Rev Cancer. 2006;6:764-775.
17. Berquin IM, Cao L, Fong D, Sloane BF. Identification of two new exons and multiple transcription start points in the 5'-untranslated region of the human cathepsin-B-encoding gene. Gene. 1995;159:143-149.
18. Arora S, Chauhan SS. Identification and characterization of a novel human cathepsin L splice variant. Gene. 2002;293:123-131.
19. Matsumoto M, Kogawa M, Wada S, Takayanagi H, Tsujimoto M, Katayama S, Hisatake K, Nogi Y. Essential role of p38 mitogen-activated protein kinase in cathepsin K gene expression during osteoclastogenesis through association of NFATc1 and PU. 1. J Biol Chem. 2004;279:45969-45979.
20. Tamura T, Thotakura P, Tanaka TS, Ko MS, Ozato K. Identification of target genes and a unique cis element regulated by IRF-8 in developing macrophages. Blood. 2005;106:1938-1947.
21. Turk B, Turk D, Salvesen GS. Regulating cysteine protease activity: essential role of protease inhibitors as guardians and regulators. Curr Pharm Des. 2002;8:1623-1637.
22. Reiser J, Adair B, Reinheckel T. Specialized roles for cysteine cathepsins in health and disease. J Clin Invest. 2010;120:3421-3431.
23. Reddy A, Caler EV, Andrews NW. Plasma membrane repair is mediated by Ca (2 +)-regulated exocytosis of lysosomes. Cell. 2001;106:157-169.
24. Cavallo-Medved D, Sloane BF. Cell-surface cathepsin B: understanding its functional significance. Curr Top Dev Biol. 2003;54:313-341.
25. Cavallo-Medved D, Dosescu J, Linebaugh BE, Sameni M, Rudy D, Sloane BF. Mutant K-ras regulates cathepsin B localization on the surface of human colorectal carcinoma cells. Neoplasia. 2003;5:507-519.
26. Cavallo-Medved D, Mai J, Dosescu J, Sameni M, Sloane BF. Caveolin-1 mediates the expression and localization of cathepsin B, pro-urokinase plasminogen activator and their cell-surface receptors in human colorectal carcinoma cells. J Cell Sci. 2005;118:1493-1503.
27. Cheng XW, Kuzuya M, Nakamura K, Di Q, Liu Z, Sasaki T, Kanda S, Jin H, Shi GP, Murohara T, Yokota M, Iguchi A. Localization of cysteine protease, cathepsin S, to the surface of vascular smooth muscle cells by association with integrin αnuβ3. Am J Pathol. 2006;168:685-694.
28. Burns-Kurtis CL, Olzinski AR, Needle S, Fox JH, Capper EA, Kelly FM, McQueney MS, Romanic AM. Cathepsin S expression is up-regulated following balloon angioplasty in the hypercholesterolemic rabbit. Cardiovasc Res. 2004;62:610-620.
29. Taleb S, Cancello R, Clement K, Lacasa D. Cathepsin s promotes human preadipocyte differentiation: possible involvement of fibronectin degradation. Endocrinology. 2006;147:4950-4959.
30. Novinec M, Grass RN, Stark WJ, Turk V, Baici A, Lenarcic B. Interaction between human cathepsins K, L, and S and elastins: mechanism of elastinolysis and inhibition by macromolecular inhibitors. J Biol Chem. 2007;282:7893-7902.
31. Hou WS, Li Z, Gordon RE, Chan K, Klein MJ, Levy R, Keysser M, Keyszer G, Bromme D. Cathepsin k is a critical protease in synovial fibroblast-mediated collagen degradation. Am J Pathol. 2001;159:2167-2177.
32. Wilson SR, Peters C, Saftig P, Bromme D. Cathepsin K activitydependent regulation of osteoclast actin ring formation and bone resorption. J Biol Chem. 2009;284:2584-2592.
33. Liu J, Sukhova GK, Sun JS, Xu WH, Libby P, Shi GP. Lysosomal cysteine proteases in atherosclerosis. Arterioscler Thromb Vasc Biol. 2004;24:1359-1366.
34. Vasiljeva O, Reinheckel T, Peters C, Turk D, Turk V, Turk B. Emerging roles of cysteine cathepsins in disease and their potential as drug targets. Curr Pharm Des. 2007;13:387-403.
35. Lutgens SP, Cleutjens KB, Daemen MJ, Heeneman S. Cathepsin cysteine proteases in cardiovascular disease. FASEB J. 2007;21:3029-3041.
36. Beers C, Honey K, Fink S, Forbush K, Rudensky A. Differential regulation of cathepsin S and cathepsin L in interferon γ-treated macrophages. J Exp Med. 2003;197:169-179.
37. Sa-Nunes A, Bafica A, Antonelli LR, Choi EY, Francischetti IM, Andersen JF, Shi GP, Chavakis T, Ribeiro JM, Kotsyfakis M. The immunomodulatory action of sialostatin L on dendritic cells reveals its potential to interfere with autoimmunity. J Immunol. 2009;182:7422-7429.
38. Shi GP, Villadangos JA, Dranoff G, Small C, Gu L, Haley KJ, Riese R, Ploegh HL, Chapman HA. Cathepsin S required for normal MHC class II peptide loading and germinal center development. Immunity. 1999;10:197-206.
39. Pierre P, Mellman I. Developmental regulation of invariant chain proteolysis controls MHC class II trafficking in mouse dendritic cells. Cell. 1998;93:1135-1145.
40. Nakagawa TY, Brissette WH, Lira PD, Griffiths RJ, Petrushova N, Stock J, McNeish JD, Eastman SE, Howard ED, Clarke SR, Rosloniec EF, Elliott EA, Rudensky AY. Impaired invariant chain degradation and antigen presentation and diminished collagen-induced arthritis in cathepsin S null mice. Immunity. 1999;10:207-217.
41. Sun J, Hartvigsen K, Chou MY, Zhang Y, Sukhova GK, Zhang J, Lopez-Ilasaca M, Diehl CJ, Yakov N, Harats D, George J, Witztum JL, Libby P, Ploegh H, Shi GP. Deficiency of antigen-presenting cell invariant chain reduces atherosclerosis in mice. Circulation. 2010;122:808-820.
42. Sasaki T, Kuzuya M, Nakamura K, Cheng XW, Hayashi T, Song H, Hu L, Okumura K, Murohara T, Iguchi A, Sato K. AT1 blockade attenuates atherosclerotic plaque destabilization accompanied by the suppression of cathepsin S activity in apoE-deficient mice. Atherosclerosis. 2010;210:430-437.
43. Cheng XW, Kuzuya M, Sasaki T, Inoue A, Hu L, Song H, Huang Z, Li P, Takeshita K, Hirashiki A, Sato K, Shi GP, Okumura K, Murohara T. Inhibition of mineralocorticoid receptor is a renoprotective effect of the 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor pitavastatin. J Hypertens. 2011;29:542-552.
44. de Nooijer R, Bot I, von der Thusen JH, Leeuwenburgh MA, Overkleeft HS, Kraaijeveld AO, Dorland R, van Santbrink PJ, van Heiningen SH, Westra MM, Kovanen PT, Jukema JW, van der Wall EE, van Berkel TJ, Shi GP, Biessen EA. Leukocyte cathepsin S is a potent regulator of both cell and matrix turnover in advanced atherosclerosis. Arterioscler Thromb Vasc Biol. 2009;29:188-194.
45. Kitamoto S, Sukhova GK, Sun J, Yang M, Libby P, Love V, Duramad P, Sun C, Zhang Y, Yang X, Peters C, Shi GP. Cathepsin L deficiency reduces diet-induced atherosclerosis in low-density lipoprotein receptorknockout mice. Circulation. 2007;115:2065-2075.
46. Libby P. Changing concepts of atherogenesis. J Intern Med. 2000;247:349-358.
47. Hummel V, Kallmann BA, Wagner S, Fuller T, Bayas A, Tonn JC, Benveniste EN, Toyka KV, Rieckmann P. Production of MMPs in human cerebral endothelial cells and their role in shedding adhesion molecules. J Neuropathol Exp Neurol. 2001;60:320-327.
48. Riese RJ, Shi GP, Villadangos J, Stetson D, Driessen C, Lennon-Dumenil AM, Chu CL, Naumov Y, Behar SM, Ploegh H, Locksley R, Chapman HA. Regulation of CD1 function and NK1.1 (+) T cell selection and maturation by cathepsin S. Immunity. 2001;15:909-919.
49. Joyce JA, Baruch A, Chehade K, Meyer-Morse N, Giraudo E, Tsai FY, Greenbaum DC, Hager JH, Bogyo M, Hanahan D. Cathepsin cysteine proteases are effectors of invasive growth and angiogenesis during multistage tumorigenesis. Cancer Cell. 2004;5:443-453.
50. Gocheva V, Zeng W, Ke D, Klimstra D, Reinheckel T, Peters C, Hanahan D, Joyce JA. Distinct roles for cysteine cathepsin genes in multistage tumorigenesis. Genes Dev. 2006;20:543-556.
51. Obermajer N, Repnik U, Jevnikar Z, Turk B, Kreft M, Kos J. Cysteine protease cathepsin X modulates immune response via activation of/32 integrins. Immunology. 2008;124:76-88.
52. Daneri-Navarro A, Del Toro-Arreola S, Sanchez-Hernandez PE, Ramirez-Duenas MG, Armendariz-Borunda J, Perez-Montfort R. Immunosuppressive activity of proteases in cervical carcinoma. Gynecol Oncol. 2005;98:111-117.
53. Alcalay NI, Sharma M, Vassmer D, Chapman B, Paul B, Zhou J, Brantley JG, Wallace DP, Maser RL, Vanden Heuvel GB. Acceleration of polycystic kidney disease progression in cpk mice carrying a deletion in the homeodomain protein Cux1. Am J Physiol Renal Physiol. 2008;295: F1725-F1734.
54. Yu W, Liu J, Shi MA, Wang J, Xiang M, Kitamoto S, Wang B, Sukhova GK, Murphy GF, Orasanu G, Grubb A, Shi GP. Cystatin C deficiency promotes epidermal dysplasia in K14-HPV16 transgenic mice. PLoS One. 2010;5: e13973.
55. Shi GP, Sukhova GK, Kuzuya M, Ye Q, Du J, Zhang Y, Pan JH, Lu ML, Cheng XW, Iguchi A, Perrey S, Lee AM, Chapman HA, Libby P. Deficiency of the cysteine protease cathepsin S impairs microvessel growth. Circ Res. 2003;92:493-500.
56. Droga-Mazovec G, Bojic L, Petelin A, Ivanova S, Romih R, Repnik U, Salvesen GS, Stoka V, Turk V, Turk B. Cysteine cathepsins trigger caspase-dependent cell death through cleavage of bid and antiapoptotic Bcl-2 homologues. J Biol Chem. 2008;283:19140-19150.
57. Li W, Yuan XM. Increased expression and translocation of lysosomal cathepsins contribute to macrophage apoptosis in atherogenesis. Ann N Y Acad Sci. 2004;1030:427-433.
58. Doran AC, Meller N, McNamara CA. Role of smooth muscle cells in the initiation and early progression of atherosclerosis. Arterioscler Thromb Vasc Biol. 2008;28:812-819.
59. Shashkin P, Dragulev B, Ley K. Macrophage differentiation to foam cells. Curr Pharm Des. 2005;11:3061-3072.
60. Oorni K, Sneck M, Bromme D, Pentikainen MO, Lindstedt KA, Mayranpaa M, Aitio H, Kovanen PT. Cysteine protease cathepsin F is expressed in human atherosclerotic lesions, is secreted by cultured macrophages, and modifies low density lipoprotein particles in vitro. J Biol Chem. 2004;279:34776-34784.
61. Sun Y, Ishibashi M, Seimon T, Lee M, Sharma SM, Fitzgerald KA, Samokhin AO, Wang Y, Sayers S, Aikawa M, Jerome WG, Ostrowski MC, Bromme D, Libby P, Tabas IA, Welch CL, Tall AR. Free cholesterol accumulation in macrophage membranes activates Toll-like receptors and p38 mitogen-activated protein kinase and induces cathepsin K. Circ Res. 2009;104:455-465.
62. Qin Y, Shi GP. Cysteinyl cathepsins and mast cell proteases in the pathogenesis and therapeutics of cardiovascular diseases. Pharmacol Ther. 2011;131:338-350.
63. Lindstedt L, Lee M, Oorni K, Bromme D, Kovanen PT. Cathepsins F and S block HDL3-induced cholesterol efflux from macrophage foam cells. Biochem Biophys Res Commun. 2003;312:1019-1024.
64. Lutgens E, Lutgens SP, Faber BC, Heeneman S, Gijbels MM, de Winther MP, Frederik P, van der Made I, Daugherty A, Sijbers AM, Fisher A, Long CJ, Saftig P, Black D, Daemen MJ, Cleutjens KB. Disruption of the cathepsin K gene reduces atherosclerosis progression and induces plaque fibrosis but accelerates macrophage foam cell formation. Circulation. 2006;113:98-107.
65. Shimizu K, Mitchell RN, Libby P. Inflammation and cellular immune responses in abdominal aortic aneurysms. Arterioscler Thromb Vasc Biol. 2006;26:987-994.
66. Henderson EL, Geng YJ, Sukhova GK, Whittemore AD, Knox J, Libby P. Death of smooth muscle cells and expression of mediators of apoptosis by T lymphocytes in human abdominal aortic aneurysms. Circulation. 1999;99:96-104.
67. Shi GP, Sukhova GK, Grubb A, Ducharme A, Rhode LH, Lee RT, Ridker PM, Libby P, Chapman HA. Cystatin C deficiency in human atherosclerosis and aortic aneurysms. J Clin Invest. 1999;104:1191-1197.
68. Aoki T, Kataoka H, Ishibashi R, Nozaki K, Hashimoto N. Cathepsin B, K, and S are expressed in cerebral aneurysms and promote the progression of cerebral aneurysms. Stroke. 2008;39:2603-2610.
69. Schulte S, Sun J, Libby P, Macfarlane L, Sun C, Lopez-Ilasaca M, Shi GP, Sukhova GK. Cystatin C deficiency promotes inflammation in angiotensin II-induced abdominal aortic aneurisms in atherosclerotic mice. Am J Pathol. 2010;177:456-463.
70. Sun J, Sukhova GK, Zhang J, Chen H, Sjoberg S, Libby P, Xia M, Xiong N, Gelb BD, Shi GP. Cathepsin K deficiency reduces elastase perfusioninduced abdominal aortic aneurysms in mice. Arterioscler Thromb Vasc Biol. In press.
71. Sun J, Sukhova GK, Zhang J, Chen H, Sjoberg S, Libby P, Xiang M, Wang J, Peters C, Reinheckel T, Shi GP. Cathepsin L activity is essential to elastase perfusion-induced abdominal aortic aneurysms in mice. Arterioscler Thromb Vasc Biol. 2011;31:2500-2508.
72. Bai L, Beckers L, Wijnands E, Lutgens SP, Herias MV, Saftig P, Daemen MJ, Cleutjens K, Lutgens E, Biessen EA, Heeneman S. Cathepsin K gene disruption does not affect murine aneurysm formation. Atherosclerosis. 2010;209:96-103.
73. Moreno PR, Purushothaman KR, Fuster V, Echeverri D, Truszczynska H, Sharma SK, Badimon JJ, O'Connor WN. Plaque neovascularization is increased in ruptured atherosclerotic lesions of human aorta: implications for plaque vulnerability. Circulation. 2004;110:2032-2038.
74. Cheng XW, Kuzuya M, Kim W, Song H, Hu L, Inoue A, Nakamura K, Di Q, Sasaki T, Tsuzuki M, Shi GP, Okumura K, Murohara T. Exercise training stimulates ischemia-induced neovascularization via phosphatidylinositol 3-kinase/Akt-dependent hypoxia-induced factor-1 αreactivation in mice of advanced age. Circulation. 2010;122:707-716.
75. Cheng XW, Kuzuya M, Nakamura K, Maeda K, Tsuzuki M, Kim W, Sasaki T, Liu Z, Inoue N, Kondo T, Jin H, Numaguchi Y, Okumura K, Yokota M, Iguchi A, Murohara T. Mechanisms underlying the impairment of ischemia-induced neovascularization in matrix metalloproteinase 2-deficient mice. Circ Res. 2007;100:904-913.
76. Cheng XW, Song H, Sasaki T, Hu L, Inoue A, Bando YK, Shi GP, Kuzuya M, Okumura K, Murohara T. Angiotensin type 1 receptor blocker reduces intimal neovascularization and plaque growth in apolipoprotein e-deficient mice. Hypertension. 2011;57:981-989.
77. Wang B, Sun J, Kitamoto S, Yang M, Grubb A, Chapman HA, Kalluri R, Shi GP. Cathepsin S controls angiogenesis and tumor growth via matrixderived angiogenic factors. J Biol Chem. 2006;281:6020-6029.
78. Urbich C, Heeschen C, Aicher A, Sasaki K, Bruhl T, Farhadi MR, Vajkoczy P, Hofmann WK, Peters C, Pennacchio LA, Abolmaali ND, Chavakis E, Reinheckel T, Zeiher AM, Dimmeler S. Cathepsin L is required for endothelial progenitor cell-induced neovascularization. Nat Med. 2005;11:206-213.
79. Sasaki T, Kuzuya M, Nakamura K, Cheng XW, Shibata T, Sato K, Iguchi A. A simple method of plaque rupture induction in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol. 2006;26:1304-1309.
80. Nakamura K, Sasaki T, Cheng XW, Iguchi A, Sato K, Kuzuya M. Statin prevents plaque disruption in apoE-knockout mouse model through pleiotropic effect on acute inflammation. Atherosclerosis. 2009;206:355-361.
81. Day SM, Reeve JL, Mundada L, Pan JH, Shi GP, Fat W. Cathepsin S-deficient imce dusplay a prothrombotic phenotype. Circulation. 2002;106:196.
82. Abedin M, Tintut Y, Demer LL. Vascular calcification: mechanisms and clinical ramifications. Arterioscler Thromb Vasc Biol. 2004;24:1161-1170.
83. Huang H, Virmani R, Younis H, Burke AP, Kamm RD, Lee RT. The impact of calcification on the biomechanical stability of atherosclerotic plaques. Circulation. 2001;103:1051-1056.
84. Aikawa E, Nahrendorf M, Figueiredo JL, Swirski FK, Shtatland T, Kohler RH, Jaffer FA, Aikawa M, Weissleder R. Osteogenesis associates with inflammation in early-stage atherosclerosis evaluated by molecular imaging in vivo. Circulation. 2007;116:2841-2850.
85. Balachandran K, Sucosky P, Jo H, Yoganathan AP. Elevated cyclic stretch alters matrix remodeling in aortic valve cusps: implications for degenerative aortic valve disease. Am J Physiol Heart Circ Physiol. 2009;296: H756-H764.
86. Qin X, Corriere MA, Matrisian LM, Guzman RJ. Matrix metalloproteinase inhibition attenuates aortic calcification. Arterioscler Thromb Vasc Biol. 2006;26:1510-1516.
87. Bouvet C, Moreau S, Blanchette J, de Blois D, Moreau P. Sequential activation of matrix metalloproteinase 9 and transforming growth factor βin arterial elastocalcinosis. Arterioscler Thromb Vasc Biol. 2008;28:856-862.
88. Aikawa E, Aikawa M, Libby P, Figueiredo JL, Rusanescu G, Iwamoto Y, Fukuda D, Kohler RH, Shi GP, Jaffer FA, Weissleder R. Arterial and aortic valve calcification abolished by elastolytic cathepsin S deficiency in chronic renal disease. Circulation. 2009;119:1785-1794.
89. Samokhin AO, Lythgo PA, Gauthier JY, Percival MD, Bromme D. Pharmacological inhibition of cathepsin S decreases atherosclerotic lesions in Apoe-/-mice. J Cardiovasc Pharmacol. 2010;56:98-105.
90. Suganuma E, Babaev VR, Motojima M, Zuo Y, Ayabe N, Fogo AB, Ichikawa I, Linton MF, Fazio S, Kon V. Angiotensin inhibition decreases progression of advanced atherosclerosis and stabilizes established atherosclerotic plaques. J Am Soc Nephrol. 2007;18:2311-2319.
91. Abisi S, Burnand KG, Humphries J, Waltham M, Taylor P, Smith A. Effect of statins on proteolytic activity in the wall of abdominal aortic aneurysms. Br J Surg. 2008;95:333-337.
92. Qin YW, Ye P, He JQ, Sheng L, Wang LY, Du J. Simvastatin inhibited cardiac hypertrophy and fibrosis in apolipoprotein E-deficient mice fed a "Western-style diet" by increasing PPAR αand γexpression and reducing TC, MMP-9, and Cat S levels. Acta Pharmacol Sin. 2010;31:1350-1358.
93. Miyake T, Aoki M, Osako MK, Shimamura M, Nakagami H, Morishita R. Systemic administration of ribbon-type decoy oligodeoxynucleotide against nuclear factor kappaB and ets prevents abdominal aortic aneurysm in rat model. Mol Ther. 2011;19:181-187.
94. Lindholt JS, Erlandsen EJ, Henneberg EW. Cystatin C deficiency is associated with the progression of small abdominal aortic aneurysms. Br J Surg. 2001;88:1472-1475.
95. Gacko M, Glowinski S. Cathepsin D and cathepsin L activities in aortic aneurysm wall and parietal thrombus. Clin Chem Lab Med. 1998;36:449-452.
96. Gacko M, Chyczewski L, Chrostek L. Distribution, activity and concentration of cathepsin B and cystatin C in the wall of aortic aneurysm. Pol J Pathol. 1999;50:83-86.
97. Zografos TA, Haliassos A, Korovesis S, Giazitzoglou E, Serelis J, Katritsis DG. Serum cathepsin levels in coronary artery ectasia. Int J Cardiol. 2010;145:606-607.
98. Liu Y, Li X, Peng D, Tan Z, Liu H, Qing Y, Xue Y, Shi GP. Usefulness of serum cathepsin L as an independent biomarker in patients with coronary heart disease. Am J Cardiol. 2009;103:476-481.