Metabolic syndrome, inflammation and atherothrombosis

Hamostaseologie

Volumn 33, Issue 4, 2013, Pages 283-294

  Rohla, M ^a   Weiss, T W ^a  

^a WILHELMINEN HOSPITAL   (Austria)

Author keywords

Atherosclerosis; Cardiovascular disease inflammation; Metabolic syndrome

Indexed keywords

ADIPOCYTOKINE; ADIPONECTIN; CARDIOTROPHIN 1; CILARY NEUROTROPHIC FACTOR; GELATINASE B; GLUCOSE; GLYCOPROTEIN; INTERLEUKIN 11; INTERLEUKIN 18; INTERLEUKIN 27; INTERLEUKIN 4; INTERLEUKIN 6; LEPTIN; LEUKEMIA INHIBITORY FACTOR; OMENTIN; ONCOSTATIN M; RESISTIN; UNCLASSIFIED DRUG;

ADIPOSE TISSUE; ANTIINFLAMMATORY ACTIVITY; ATHEROSCLEROTIC PLAQUE; CALORIC INTAKE; CARDIOVASCULAR DISEASE; CARDIOVASCULAR RISK; CEREBROVASCULAR ACCIDENT; CROSS LINKING; DIABETES MELLITUS; FAMILY HISTORY; FRAMINGHAM RISK SCORE; HEART INFARCTION; HUMAN; HYPERCHOLESTEROLEMIA; HYPERGLYCEMIA; HYPERTENSION; IMPAIRED GLUCOSE TOLERANCE; INFLAMMATORY DISEASE; METABOLIC SYNDROME X; PATHOGENESIS; PHYSICAL INACTIVITY; REVIEW; SMOKING; SUDDEN CARDIAC DEATH; THROMBOCYTE; THROMBOSIS;

ATHEROSCLEROSIS; CARDIOVASCULAR DISEASE INFLAMMATION; METABOLIC SYNDROME;

ANIMALS; ATHEROSCLEROSIS; CYTOKINES; HUMANS; INFLAMMATION; METABOLIC SYNDROME X; MODELS, CARDIOVASCULAR; MODELS, IMMUNOLOGICAL; THROMBOSIS;

EID: 84888394950     PISSN: 07209355     EISSN: None     Source Type: Journal    
DOI: 10.5482/HAMO-13-07-0035     Document Type: Review

References (148)

1. Go AS, Mozaffarian D, Roger VL et al. Heart disease and stroke statistics--2013 update: a report from the American Heart Association. Circulation 2013; 127: e6-e245.
2. Kannel WB, McGee D, Gordon T. A general cardiovascular risk profile: the Framingham Study. Am J Cardiol 1976;3 8: 46-51.
3. Finkelstein EA, Khavjou OA, Thompson H et al. Obesity and severe obesity forecasts through 2030. Am J Prev Med 2012; 42: 563-570.
4. Wilson PW, Castelli WP, Kannel WB. Coronary risk prediction in adults (the Framingham Heart Study). Am J Cardiol 1987; 59: 91G-94G.
5. Grundy SM. Metabolic syndrome pandemic. Arteriosclerosis, thrombosis, and vascular biology 2008; 28: 629-636.
6. Alberti KG, Zimmet P, Shaw J. The metabolic syndrome--a new worldwide definition. Lancet 2005; 366: 1059-1062.
7. Grundy SM, Cleeman JI, Daniels SR et al. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation 2005; 112: 2735-2752.
8. Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med 1998; 15: 539-553.
9. Einhorn D, Reaven GM, Cobin RH et al. American College of Endocrinology position statement on the insulin resistance syndrome. Endocr Pract 2003; 9: 237-252.
10. Balkau B, Charles MA. Comment on the provisional report from the WHO consultation. European Group for the Study of Insulin Resistance (EGIR). Diabet Med 1999; 16: 442-443.
11. Trøseid M. Studies on inflammation and atherosclerosis in the metabolic syndrome. Doktoravhandling, University of Oslo 2010.
12. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA 2001; 285: 2486-2497.
13. Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 1988; 37: 1595-1607.
14. Despres JP, Lemieux I, Bergeron J et al. Abdominal obesity and the metabolic syndrome: contribution to global cardiometabolic risk. Arterioscler Thromb Vasc Biol 2008; 28: 1039-1049.
15. Nilsson PM, Engstrom G, Hedblad B. The metabolic syndrome and incidence of cardiovascular disease in non-diabetic subjects - a populationbased study comparing three different definitions. Diabet Med 2007; 24: 464-472.
16. Paras E, Mancini GB, Lear SA. The relationship of three common definitions of the metabolic syndrome with sub-clinical carotid atherosclerosis. Atherosclerosis 2008; 198: 228-236.
17. Sandhofer A, Iglseder B, Paulweber B et al. Comparison of different definitions of the metabolic syndrome. Eur J Clin Invest 2007; 37: 109-116.
18. Levitan EB, Song Y, Ford ES, Liu S. Is nondiabetic hyperglycemia a risk factor for cardiovascular disease? A meta-analysis of prospective studies. Arch Intern Med 2004; 164: 2147-2155.
19. Rexrode KM, Carey VJ, Hennekens CH et al. Abdominal adiposity and coronary heart disease in women. JAMA 1998; 280: 1843-1848.
20. Lewington S, Clarke R, Qizilbash N et al. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 2002; 360: 1903-1913.
21. Sarwar N, Danesh J, Eiriksdottir G et al. Triglycerides and the risk of coronary heart disease: 10,158 incident cases among 262,525 participants in 29 Western prospective studies. Circulation 2007; 115: 450-458.
22. Castelli WP, Garrison RJ, Wilson PW et al. Incidence of coronary heart disease and lipoprotein cholesterol levels. The Framingham Study. JAMA 1986; 256: 2835-2838.
23. Kahn R. Metabolic syndrome: is it a syndrome? Does it matter? Circulation 2007; 115: 1806-1811.
24. Grundy SM. Does the metabolic syndrome exist? Diabetes Care 2006; 29: 1689-1692.
25. Hunt KJ, Resendez RG, Williams K et al. National Cholesterol Education Program versus World Health Organization metabolic syndrome in relation to all-cause and cardiovascular mortality in the San Antonio Heart Study. Circulation 2004; 110: 1251-1257.
26. Tenenbaum A, Fisman EZ. "The metabolic syndrome... is dead": these reports are an exaggeration. Cardiovasc Diabetol 2011; 10: 11.
27. Feinberg MS, Schwartz R, Tanne D et al. Impact of the metabolic syndrome on the clinical outcomes of non-clinically diagnosed diabetic patients with acute coronary syndrome. Am J Cardiol 2007; 99: 667-672.
28. Wilson PW, D'Agostino RB, Parise H et al. Metabolic syndrome as a precursor of cardiovascular disease and type 2 diabetes mellitus. Circulation. 2005;112: 3066-3072.
29. Haffner SM, Stern MP, Hazuda HP et al. Cardiovascular risk factors in confirmed prediabetic individuals. Does the clock for coronary heart disease start ticking before the onset of clinical diabetes? JAMA 1990; 263: 2893-2898.
30. Eckel RH, Grundy SM, Zimmet PZ. The metabolic syndrome. Lancet 2005; 365: 1415-1428.
31. Kullo IJ, Cassidy AE, Peyser PA et al. Association between metabolic syndrome and subclinical coronary atherosclerosis in asymptomatic adults. Am J Cardiol 2004; 94: 1554-1558.
32. Ingelsson E, Sullivan LM, Murabito JM et al. Prevalence and prognostic impact of subclinical cardiovascular disease in individuals with the metabolic syndrome and diabetes. Diabetes 2007; 56: 1718-1726.
33. Derosa G, D'Angelo A, Tinelli C et al. Evaluation of metalloproteinase 2 and 9 levels and their inhibitors in diabetic and healthy subjects. Diabetes Metab 2007; 33: 129-134.
34. Gami AS, Witt BJ, Howard DE et al. Metabolic syndrome and risk of incident cardiovascular events and death: a systematic review and metaanalysis of longitudinal studies. J Am Coll Cardiol 2007; 49: 403-414.
35. Okosun IS, Chandra KM, Boev A et al. Abdominal adiposity in U.S. adults: prevalence and trends, 1960-2000. Prev Med 2004; 39: 197-206.
36. Li C, Ford ES, McGuire LC, Mokdad AH. Increasing trends in waist circumference and abdominal obesity among US adults. Obesity (Silver Spring) 2007; 15: 216-224.
37. Ford ES, Giles WH, Mokdad AH. Increasing prevalence of the metabolic syndrome among U.S. adults. Diabetes Care 2004; 27: 2444-2449.
38. Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA 2002; 287: 356-359.
39. Graham I, Atar D, Borch-Johnsen K et al. European guidelines on cardiovascular disease prevention in clinical practice. Eur J Cardiovasc Prev Rehabil 2007;14 (Suppl 2): S1-S113.
40. James PT, Rigby N, Leach R. The obesity epidemic, metabolic syndrome and future prevention strategies. Eur J Cardiovasc Prev Rehabil 2004; 11: 3-8.
41. Ross R. Atherosclerosis is an inflammatory disease. Am Heart J 1999; 138: S419-S420.
42. Libby P. Inflammation in atherosclerosis. Nature 2002; 420: 868-874.
43. Packard RR, Libby P. Inflammation in atherosclerosis: from vascular biology to biomarker discovery and risk prediction. Clin Chem 2008; 54: 24-38.
44. Rocha VZ, Libby P. Obesity, inflammation, and atherosclerosis. Nat Rev Cardiol 2009; 6: 399-409.
45. Steffens S, Mach F. Inflammation and atherosclerosis. Herz 2004; 29: 741-748.
46. Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 2005; 352: 1685-1695.
47. Luchtefeld M, Schunkert H, Stoll M et al. Signal transducer of inflammation gp130 modulates atherosclerosis in mice and man. J Exp Med 2007; 204: 1935-1944.
48. Marrone D, Pertosa G, Simone S et al. Local activation of interleukin 6 signaling is associated with arteriovenous fistula stenosis in hemodialysis patients. Am J Kidney Dis 2007; 49: 664-673.
49. Scheller J, Rose-John S. Interleukin-6 and its receptor: from bench to bedside. Med Microbiol Immunol 2006; 195: 173-183.
50. Schuett H, Luchtefeld M, Grothusen C et al. How much is too much? Interleukin-6 and its signalling in atherosclerosis. Thromb Haemost 2009; 102: 215-222.
51. Taga T, Kishimoto T. Gp130 and the interleukin-6 family of cytokines. Annu Rev Immunol 1997; 15: 797-819.
52. Moran CS, Campbell JH, Campbell GR. Human leukemia inhibitory factor upregulates LDL receptors on liver cells and decreases serum cholesterol in the cholesterol-fed rabbit. Arterioscler Thromb Vas Biol 1997; 17: 1267-1273.
53. Moran CS, Campbell JH, Campbell GR. Induction of smooth muscle cell nitric oxide synthase by human leukaemia inhibitory factor: effects in vitro and in vivo. J Vasc Res 1997; 34: 378-385.
54. Moran CS, Campbell JH, Simmons DL, Campbell GR. Human leukemia inhibitory factor inhibits development of experimental atherosclerosis. Arterioscler Thromb 1994; 14: 1356-1363.
55. Rolfe BE, Stamatiou S, World CJ et al. Leukaemia inhibitory factor retards the progression of atherosclerosis. Cardiovasc Res 2003; 58: 222-230.
56. Seino Y, Ikeda U, Ikeda M et al. Interleukin 6 gene transcripts are expressed in human atherosclerotic lesions. Cytokine 1994; 6: 87-91.
57. Weiss TW, Samson AL, Niego B et al. Oncostatin M is a neuroprotective cytokine that inhibits excitotoxic injury in vitro and in vivo. FASEB J 2006; 20: 2369-2371.
58. Nakanishi K, Yoshimoto T, Tsutsui H, Okamura H. Interleukin-18 is a unique cytokine that stimulates both Th1 and Th2 responses depending on its cytokine milieu. Cytokine Growth Factor Rev 2001; 12: 53-72.
59. Mallat Z, Corbaz A, Scoazec A et al. Expression of interleukin-18 in human atherosclerotic plaques and relation to plaque instability. Circulation 2001; 104: 1598-1603.
60. Robertson AK, Hansson GK. T cells in atherogenesis: for better or for worse? Arterioscler Thromb Vasc Biol 2006; 26: 2421-2432.
61. Leon ML, Zuckerman SH. Gamma interferon: a central mediator in atherosclerosis. Inflamm Res 2005; 54: 395-411.
62. Blankenberg S, Luc G, Ducimetiere P et al. Interleukin-18 and the risk of coronary heart disease in European men: the Prospective Epidemiological Study of Myocardial Infarction (PRIME). Circulation 2003; 108: 2453-2459.
63. Koenig W, Khuseyinova N, Baumert J et al. Increased concentrations of C-reactive protein and IL-6 but not IL-18 are independently associated with incident coronary events in middle-aged men and women: results from the MONICA/KORA Augsburg case-cohort study, 1984-2002. Arterioscler Thromb Vasc Biol 2006; 26: 2745-2751.
64. Carmeliet P, Collen D. Development and disease in proteinase-deficient mice: role of the plasminogen, matrix metalloproteinase and coagulation system. Thromb Res 1998; 91: 255-285.
65. Malemud CJ. Matrix metalloproteinases (MMPs) in health and disease: an overview. Front Biosci 2006; 11: 1696-1701.
66. Lijnen HR. Elements of the fibrinolytic system. Ann N York Acad Sci 2001; 936: 226-236.
67. Newby AC, George SJ, Ismail Y et al. Vulnerable atherosclerotic plaque metalloproteinases and foam cell phenotypes. Thromb Haemost 2009; 101: 1006-1011.
68. Newby AC. Metalloproteinases and vulnerable atherosclerotic plaques. Trends Cardiovasc Med 2007; 17: 253-258.
69. Konstantino Y, Nguyen TT, Wolk R et al. Potential implications of matrix metalloproteinase-9 in assessment and treatment of coronary artery disease. Biomarkers 2009; 14: 118-129.
70. Libby P, Aikawa M. Stabilization of atherosclerotic plaques: new mechanisms and clinical targets. Nat Med 2002; 8: 1257-1262.
71. Hernandez-Presa M, Bustos C, Ortego M et al. Angiotensin-converting enzyme inhibition prevents arterial nuclear factor-kappa B activation, monocyte chemoattractant protein-1 expression, and macrophage infiltration in a rabbit model of early accelerated atherosclerosis. Circulation 1997; 95: 1532-1541.
72. Hajer GR, van Haeften TW, Visseren FL. Adipose tissue dysfunction in obesity, diabetes, and vascular diseases. Eur Heart J 2008; 29: 2959-2971.
73. Vaughan DE. PAI-1 and atherothrombosis. J Thromb Haemost 2005; 3: 1879-1883.
74. 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: 1579-1585.
75. Macfelda K, Weiss TW, Kaun C et al. Plasminogen activator inhibitor 1 expression is regulated by the inflammatory mediators interleukin-1alpha, tumor necrosis factor-alpha, transforming growth factor-beta and oncostatin M in human cardiac myocytes. J Mol Cell Cardiol 2002; 34: 1681-1691.
76. Rega G, Kaun C, Weiss TW et al. Inflammatory cytokines interleukin-6 and oncostatin m induce plasminogen activator inhibitor-1 in human adipose tissue. Circulation 2005; 111: 1938-1945.
77. Berg AH, Scherer PE. Adipose tissue, inflammation, and cardiovascular disease. Circ Res 2005; 96: 939-949.
78. Bouloumie A, Sengenes C, Portolan G et al. Adipocyte produces matrix metalloproteinases 2 and 9: involvement in adipose differentiation. Diabetes 2001; 50: 2080-2086.
79. Kim SY, Park SM, Lee ST. Apolipoprotein C-II is a novel substrate for matrix metalloproteinases. Biochem Biophys Res Commun 2006; 339: 47-54.
80. Furenes EB, Seljeflot I, Solheim S et al. Long-term influence of diet and/or omega-3 fatty acids on matrix metalloproteinase-9 and pregnancy-associated plasma protein-A in men at high risk of coronary heart disease. Scand J Clin Lab Invest 2008; 68: 177-184.
81. Koh KK, Son JW, Ahn JY et al. Non-lipid effects of statin on hypercholesterolemic patients established to have coronary artery disease who remained hypercholesterolemic while eating a step-II diet. Coron Artery Dis 2001; 12: 305-311.
82. Kalela A, Koivu TA, Hoyhtya M et al. Association of serum MMP-9 with autoantibodies against oxidized LDL. Atherosclerosis 2002; 160: 161-165.
83. Weiss TW, Seljeflot I, Hjerkinn EM, Arnesen H. Adipose tissue pro-inflammatory gene expression is associated with cardiovascular disease. Int J Clin Pract 2011; 65: 939-944.
84. Sattar N, Wannamethee G, Sarwar N et al. Leptin and coronary heart disease: prospective study and systematic review. J Am Coll Cardiol 2009; 53: 167-175.
85. Piatti P, Di Mario C, Monti LD et al. Association of insulin resistance, hyperleptinemia, and impaired nitric oxide release with in-stent restenosis in patients undergoing coronary stenting. Circulation 2003; 108: 2074-2081.
86. Lawlor DA, Smith GD, Kelly A et al. Leptin and coronary heart disease risk: prospective case control study of British women. Obesity 2007; 15: 1694-1701.
87. Zhang Y, Proenca R, Maffei M et al. Positional cloning of the mouse obese gene and its human homologue. Nature 1994; 372: 425-432.
88. Pelleymounter MA, Cullen MJ, Baker MB et al. Effects of the obese gene product on body weight regulation in ob/ob mice. Science 1995; 269: 540-543.
89. Friedman JM. Leptin, leptin receptors, and the control of body weight. Nutr Rev 1998; 56: s38-s46.
90. Gualillo O, Gonzalez-Juanatey JR, Lago F. The emerging role of adipokines as mediators of cardiovascular function: physiologic and clinical perspectives. Trends Cardiovasc Med 2007; 17: 275-283.
91. Friedman JM, Halaas JL. Leptin and the regulation of body weight in mammals. Nature 1998; 395: 763-770.
92. Heymsfield SB, Greenberg AS, Fujioka K et al. Recombinant leptin for weight loss in obese and lean adults: a randomized, controlled, dose-escalation trial. JAMA 1999; 282: 1568-1575.
93. Maffei M, Halaas J, Ravussin E et al. Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nat Med 1995; 1: 1155-1161.
94. Moon HS, Matarese G, Brennan AM et al. Efficacy of metreleptin in obese patients with type 2 diabetes: cellular and molecular pathways underlying leptin tolerance. Diabetes 2011; 60: 1647-1656.
95. Vatier C, Gautier JF, Vigouroux C. Therapeutic use of recombinant methionyl human leptin. Biochimie 2012; 94: 2116-2125.
96. Von Eynatten M, Humpert PM, Bluemm A et al. High-molecular weight adiponectin is independently associated with the extent of coronary artery disease in men. Atherosclerosis 2008; 199: 123-128.
97. Salmenniemi U, Ruotsalainen E, Pihlajamaki J et al. Multiple abnormalities in glucose and energy metabolism and coordinated changes in levels of adiponectin, cytokines, and adhesion molecules in subjects with metabolic syndrome. Circulation 2004; 110: 3842-3848.
98. Kubota N, Terauchi Y, Yamauchi T et al. Disruption of adiponectin causes insulin resistance and neointimal formation. J Biol Chem 2002; 277: 25863-25866.
99. Matsuda M, Shimomura I, Sata M et al. Role of adiponectin in preventing vascular stenosis. The missing link of adipo-vascular axis. J Biol Chem 2002; 277: 37487-37491.
100. Kistorp C, Faber J, Galatius S et al. Plasma adiponectin, body mass index, and mortality in patients with chronic heart failure. Circulation 2005; 112: 1756-1762.
101. Kumada M, Kihara S, Ouchi N et al. Adiponectin specifically increased tissue inhibitor of metalloproteinase-1 through interleukin-10 expression in human macrophages. Circulation 2004; 109: 2046-2049.
102. Shimada K, Miyauchi K, Mokuno H et al. Predictive value of the adipocyte-derived plasma protein adiponectin for restenosis after elective coronary stenting. Jpn Heart J 2002; 43: 85-91.
103. Hong SJ, Shim WJ, Choi JI et al. Comparison of effects of telmisartan and valsartan on late lumen loss and inflammatory markers after sirolimuseluting stent implantation in hypertensive patients. Am J Cardiol 2007; 100: 1625-1629.
104. Tan BK, Adya R, Randeva HS. Omentin: a novel link between inflammation, diabesity, and cardiovascular disease. Trends Cardiovasc Med 2010; 20: 143-148.
105. Tan BK, Adya R, Farhatullah S et al. Metformin treatment may increase omentin-1 levels in women with polycystic ovary syndrome. Diabetes 2010; 59: 3023-3031.
106. Lewandowski K, Nadel I, Lewinski A et al. Positive correlation between serum omentin and thrombospondin-1 in gestational diabetes despite lack of correlation with insulin resistance indices. Ginekologia polska 2010; 81: 907-912.
107. Duan XY, Xie PL, Ma YL, Tang SY. Omentin inhibits osteoblastic differentiation of calcifying vascular smooth muscle cells through the PI3K/Akt pathway. Amino acids 2011; 41: 1223-1231.
108. Liu R, Wang X, Bu P. Omentin-1 is associated with carotid atherosclerosis in patients with metabolic syndrome. Diabetes Res Clin Pract 2011; 93: 21-25.
109. Yamawaki H, Kuramoto J, Kameshima S et al. Omentin, a novel adipocytokine inhibits TNF-induced vascular inflammation in human endothelial cells. Biochem Biophys Res Commun 2011; 408: 339-343.
110. Boyraz M, Cekmez F, Karaoglu A et al. Relationship of adipokines (adiponectin, resistin and RBP4) with metabolic syndrome components in pubertal obese children. Biomark Med 2013; 7: 423-428.
111. Perez PM, Moore-Carrasco R, Gonzalez DR et al. Gene expression of adipose tissue, endothelial cells and platelets in subjects with metabolic syndrome. Mol Med Rep 2012; 5: 1135-1140.
112. Verma S, Li SH, Wang CH et al. Resistin promotes endothelial cell activation: further evidence of adipokine-endothelial interaction. Circulation 2003; 108: 736-740.
113. On YK, Park HK, Hyon MS, Jeon ES. Serum resistin as a biological marker for coronary artery disease and restenosis in type 2 diabetic patients. Circ J 2007; 71: 868-873.
114. Gwechenberger M, Pacher R, Berger R et al. Comparison of soluble glycoprotein 130 and cardiac natriuretic peptides as long-term predictors of heart failure progression. J Heart Lung Transplant 2005; 24: 2190-2195.
115. Deten A, Volz HC, Briest W, Zimmer HG. Cardiac cytokine expression is upregulated in the acute phase after myocardial infarction. Experimental studies in rats. Cardiovasc Res 2002; 55: 329-340.
116. Weiss TW, Arnesen H, Seljeflot I. Components of the Interleukin-6 transsignalling system are associated with the metabolic syndrome, endothelial dysfunction and arterial stiffness. Metabolism 2013; 62: 1008-1013.
117. Gnacinska M, Malgorzewicz S, Stojek M et al. Role of adipokines in complications related to obesity: a review. Adv Med Sci 2009; 54: 150-157.
118. Sun J, Xu Y, Dai Z, Sun Y. Intermittent high glucose stimulate MCP-l, IL-18, and PAI-1, but inhibit adiponectin expression and secretion in adipocytes dependent of ROS. Cell Biochem Biophys 2009; 55: 173-180.
119. Troseid M, Seljeflot I, Hjerkinn EM, Arnesen H. Interleukin-18 is a strong predictor of cardiovascular events in elderly men with the metabolic syndrome: synergistic effect of inflammation and hyperglycemia. Diabetes Care 2009; 32: 486-492.
120. Hung J, McQuillan BM, Chapman CM et al. Elevated interleukin-18 levels are associated with the metabolic syndrome independent of obesity and insulin resistance. Arterioscler Thromb Vasc Biol 2005; 25: 1268-1273.
121. Thorand B, Kolb H, Baumert J et al. Elevated levels of interleukin-18 predict the development of type 2 diabetes: results from the MONICA/ KORA Augsburg Study, 1984-2002. Diabetes 2005; 54: 2932-2938.
122. Weiss TW, Arnesen H, Troseid M et al. Adipose tissue expression of interleukin-18 mRNA is elevated in subjects with metabolic syndrome and independently associated with fasting glucose. Wien Klin Wochenschrift 2011; 123: 650-654.
123. Sierevogel MJ, Pasterkamp G, de Kleijn DP, Strauss BH. Matrix metalloproteinases: a therapeutic target in cardiovascular disease. Curr Pharm Des 2003; 9: 1033-1040.
124. Rydlova M, Holubec L Jr, Ludvikova M Jr et al. Biological activity and clinical implications of the matrix metalloproteinases. Anticancer Res 2008; 28: 1389-1397.
125. De Nooijer R, Verkleij CJ, von der Thusen 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: 340-346.
126. Derosa G, Cicero AF, Scalise F et al. Metalloproteinase-2 and -9 in diabetic and nondiabetic subjects during acute coronary syndromes. Endothelium 2007; 14: 45-51.
127. Derosa G, D'Angelo A, Ciccarelli L et al. Matrix metalloproteinase-2, -9, and tissue inhibitor of metalloproteinase-1 in patients with hypertension. Endothelium 2006; 13: 227-231.
128. El Messal M, Beaudeux JL, Drissi A et al. Elevated serum levels of proinflammatory cytokines and biomarkers of matrix remodeling in never-treated patients with familial hypercholesterolemia. Clin Chim Acta 2006; 366: 185-189.
129. Weiss TW, Furenes EB, Troseid M et al. Prediction of cardiovascular events by matrix metalloproteinase (MMP)-9 in elderly men. Thromb Haemost 103: 679-681.
130. Murad MH, Hazem A, Coto-Yglesias F et al. The association of hypertriglyceridemia with cardiovascular events and pancreatitis: a systematic review and meta-analysis. BMC Endocr Disord 2012; 12:2. doi: 10.1186/1472-6823-12-2.
131. Hidalgo M, Eckhardt SG. Development of matrix metalloproteinase inhibitors in cancer therapy. J Natl Cancer Inst 2001; 93: 178-193.
132. Hidalgo M, Eckhardt SG. Matrix metalloproteinase inhibitors: how can we optimize their development? Ann Oncol 2001; 12: 285-287.
133. Crompton MR. Retinal emboli in stenosis of the internal carotid artery. Lancet 1963; 1: 886.
134. Lindemann S, Kramer B, Seizer P, Gawaz M. Platelets, inflammation and atherosclerosis. J Thromb Haemost 2007; 5 (Suppl 1): 203-211.
135. Frenette PS, Johnson RC, Hynes RO, Wagner DD. Platelets roll on stimulated endothelium in vivo: an interaction mediated by endothelial P-selectin. Proc Natl Acad Sci USA 1995; 92: 7450-7454.
136. Massberg S, Enders G, Leiderer R et al. Plateletendothelial cell interactions during ischemia/reperfusion: the role of P-selectin. Blood 1998; 92: 507-515.
137. Lindemann S, Tolley ND, Dixon DA et al. Activated platelets mediate inflammatory signaling by regulated interleukin 1beta synthesis. J Cell Biol 2001; 154: 485-490.
138. Chironi G, Simon A, Hugel B et al. Circulating leukocyte-derived microparticles predict subclinical atherosclerosis burden in asymptomatic subjects. Arterioscler Thromb Vasc Biol 2006; 26: 2775-2780.
139. Massberg S, Konrad I, Schurzinger K et al. Platelets secrete stromal cell-derived factor 1alpha and recruit bone marrow-derived progenitor cells to arterial thrombi in vivo. J Exp Med 2006; 203: 1221-1233.
140. Stellos K, Bigalke B, Langer H et al. Expression of stromal-cell-derived factor-1 on circulating platelets is increased in patients with acute coronary syndrome and correlates with the number of CD34+ progenitor cells. Eur Heart J 2009; 30: 584-593.
141. Daub K, Langer H, Seizer P et al. Platelets induce differentiation of human CD34+ progenitor cells into foam cells and endothelial cells. FASEB J 2006; 20: 2559-2561.
142. O'Donoghue ML, Braunwald E, White HD et al. Study design and rationale for the Stabilization of pLaques usIng Darapladib-Thrombolysis in Myocardial Infarction (SOLID-TIMI 52) trial in patients after an acute coronary syndrome. Am Heart J 2011; 162: 613-619.e1.
143. White H, Held C, Stewart R et al. Study design and rationale for the clinical outcomes of the STABILITY Trial (STabilization of Atherosclerotic plaque By Initiation of darapLadIb TherapY) comparing darapladib versus placebo in patients with coronary heart disease. Am Heart J 2010; 160: 655-661.
144. Njerve IU, Weiss TW, Arnesen H. Saxagliptin and Atherosclerosis (SAXATH). www.clinical.gov.
145. Zucker S, Cao J. Selective matrix metalloproteinase (MMP) inhibitors in cancer therapy: ready for prime time? Cancer Biol Ther 2009; 8: 2371-2373.
146. 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: 528-535.
147. Devel L, Garcia S, Czarny B et al. Insights from selective non-phosphinic inhibitors of MMP-12 tailored to fit with an S1' loop canonical conformation. J Biol Chem 2010; 285: 35900-35909.
148. Dorman G, Kocsis-Szommer K, Spadoni C, Ferdinandy P. MMP inhibitors in cardiac diseases: an update. Recent Pat Cardiovasc Drug Discov 2007; 2: 186-194.