Role of Lipotoxicity in Endothelial Dysfunction

Heart Failure Clinics

Volumn 8, Issue 4, 2012, Pages 589-607

  Kim, Jeong A ^a,b   Montagnani, Monica ^c   Chandrasekran, Sruti ^d   Quon, Michael J ^d  

^a University of Alabama at Birmingham   (United States)

^b UNIVERSITY OF ALABAMA AT BIRMINGHAM   (United States)

^c UNIVERSITY OF BARI   (Italy)

^d UNIVERSITY OF MARYLAND SCHOOL OF MEDICINE   (United States)

Author keywords

Cardiovascular disease; Endothelial dysfunction; Lipotoxicity; Metabolic disorders

Indexed keywords

2,4 THIAZOLIDINEDIONE DERIVATIVE; ACIPIMOX; ALEGLITAZAR; ANGIOTENSIN RECEPTOR ANTAGONIST; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; BEZAFIBRATE; CIPROFIBRATE; CLOFIBRATE; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; EZETIMIBE; FATTY ACID; FENOFIBRATE; FENOFIBRATE PLUS PRAVASTATIN; GEMFIBROZIL; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INSULIN; MURAGLITAZAR; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR AGONIST; PIOGLITAZONE; PLACEBO; RAGAGLITAZAR; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE; ROSIGLITAZONE; SIMVASTATIN; STATIN; STRESS ACTIVATED PROTEIN KINASE; TAMOXIFEN; TESAGLITAZAR; THERMOZYMOCIDIN; UNINDEXED DRUG;

APOPTOSIS; CARDIOMYOPATHY; CHOLESTEROL BLOOD LEVEL; DIABETES MELLITUS; DYSLIPIDEMIA; ENDOPLASMIC RETICULUM STRESS; ENDOTHELIAL DYSFUNCTION; EXERCISE; FATTY ACID BLOOD LEVEL; HUMAN; HYPERLIPIDEMIA; INFLAMMATION; ISCHEMIC HEART DISEASE; KIDNEY DISEASE; LIPOTOXICITY; NEUROPATHY; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OBESITY; OXIDATIVE STRESS; REVIEW;

APOPTOSIS; CARDIOMYOPATHIES; ENDOPLASMIC RETICULUM; ENDOTHELIUM, VASCULAR; FIBRIC ACIDS; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; HYPERLIPIDEMIAS; INFLAMMATION; MITOCHONDRIAL DISEASES; OXIDATIVE STRESS; TRIGLYCERIDES;

EID: 84866595435     PISSN: 15517136     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.hfc.2012.06.012     Document Type: Review

References (265)

1. Kim J.A., Montagnani M., Koh K.K., et al. Reciprocal relationships between insulin resistance and endothelial dysfunction: molecular and pathophysiological mechanisms. Circulation 2006, 113(15):1888-1904.
2. Marks J.B., Raskin P. Cardiovascular risk in diabetes: a brief review. J Diabet Complications 2000, 14(2):108-115.
3. Rubanyi G.M. Endothelium-derived relaxing and contracting factors. J Cell Biochem 1991, 46(1):27-36.
4. Aggoun Y. Obesity, metabolic syndrome, and cardiovascular disease. Pediatr Res 2007, 61(6):653-659.
5. DeFronzo R.A. Insulin resistance, lipotoxicity, type 2 diabetes and atherosclerosis: the missing links. The Claude Bernard lecture 2009. Diabetologia 2010, 53(7):1270-1287.
6. van de Weijer T., Schrauwen-Hinderling V.B., Schrauwen P. Lipotoxicity in type 2 diabetic cardiomyopathy. Cardiovasc Res 2011, 92(1):10-18.
7. Duncan J.G. Lipotoxicity: what is the fate of fatty acids?. J Lipid Res 2008, 49(7):1375-1376.
8. Steinberg H.O., Chaker H., Leaming R., et al. Obesity/insulin resistance is associated with endothelial dysfunction. Implications for the syndrome of insulin resistance. J Clin Invest 1996, 97(11):2601-2610.
9. Berg A.H., Scherer P.E. Adipose tissue, inflammation, and cardiovascular disease. Circ Res 2005, 96(9):939-949.
10. Nordestgaard B.G., Benn M., Schnohr P., et al. Nonfasting triglycerides and risk of myocardial infarction, ischemic heart disease, and death in men and women. JAMA 2007, 298(3):299-308.
11. 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(4):450-458.
12. Abe H., Yamada N., Kamata K., et al. Hypertension, hypertriglyceridemia, and impaired endothelium-dependent vascular relaxation in mice lacking insulin receptor substrate-1. J Clin Invest 1998, 101(8):1784-1788.
13. Johansen C.T., Wang J., Lanktree M.B., et al. Excess of rare variants in genes identified by genome-wide association study of hypertriglyceridemia. Nat Genet 2010, 42(8):684-687.
14. Dallinga-Thie G.M., Franssen R., Mooij H.L., et al. The metabolism of triglyceride-rich lipoproteins revisited: new players, new insight. Atherosclerosis 2010, 211(1):1-8.
15. Surendran R.P., Visser M.E., Heemelaar S., et al. Mutations in LPL, APOC2, APOA5, GPIHBP1 and LMF1 in patients with severe hypertriglyceridaemia. J Intern Med 2012, [Epub ahead of print]. 10.1111/j.1365-2796.2012.02516.x.
16. Young S.G., Davies B.S., Voss C.V., et al. GPIHBP1, an endothelial cell transporter for lipoprotein lipase. J Lipid Res 2011, 52(11):1869-1884.
17. van de Woestijne A.P., Monajemi H., Kalkhoven E., et al. Adipose tissue dysfunction and hypertriglyceridemia: mechanisms and management. Obesity 2011, 12(10):829-840.
18. Unger R.H. Minireview: weapons of lean body mass destruction: the role of ectopic lipids in the metabolic syndrome. Endocrinology 2003, 144(12):5159-5165.
19. Hokanson J.E., Austin M.A. Plasma triglyceride level is a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol level: a meta-analysis of population-based prospective studies. J Cardiovasc Risk 1996, 3(2):213-219.
20. Xiang G.D., Xiang L.W., He H.L., et al. Postprandial lipaemia suppresses endothelium-dependent arterial dilation in patients with hypothyroidism. Endocrine 2012 Feb 22, [Epub ahead of print].
21. Yunoki K., Nakamura K., Miyoshi T., et al. Impact of hypertriglyceridemia on endothelial dysfunction during statin +/- ezetimibe therapy in patients with coronary heart disease. Am J Cardiol 2011, 108(3):333-339.
22. Yunoki K., Nakamura K., Miyoshi T., et al. Ezetimibe improves postprandial hyperlipemia and its induced endothelial dysfunction. Atherosclerosis 2011, 217(2):486-491.
23. Kastelein J.J., Akdim F., Stroes E.S., et al. Simvastatin with or without ezetimibe in familial hypercholesterolemia. N Engl J Med 2008, 358(14):1431-1443.
24. Alipour A., van Oostrom A.J., Izraeljan A., et al. Leukocyte activation by triglyceride-rich lipoproteins. Arterioscler Thromb Vasc Biol 2008, 28(4):792-797.
25. Schwartz E.A., Reaven P.D. Lipolysis of triglyceride-rich lipoproteins, vascular inflammation, and atherosclerosis. Biochim Biophys Acta 2012, 1821(5):858-866. [Epub 2011 Oct 7].
26. van Oostrom A.J., Sijmonsma T.P., Verseyden C., et al. Postprandial recruitment of neutrophils may contribute to endothelial dysfunction. J Lipid Res 2003, 44(3):576-583.
27. Sinha R., Dufour S., Petersen K.F., et al. Assessment of skeletal muscle triglyceride content by (1)H nuclear magnetic resonance spectroscopy in lean and obese adolescents: relationships to insulin sensitivity, total body fat, and central adiposity. Diabetes 2002, 51(4):1022-1027.
28. Virkamaki A., Korsheninnikova E., Seppala-Lindroos A., et al. Intramyocellular lipid is associated with resistance to in vivo insulin actions on glucose uptake, antilipolysis, and early insulin signaling pathways in human skeletal muscle. Diabetes 2001, 50(10):2337-2343.
29. Inoue T., Kobayashi K., Inoguchi T., et al. Reduced expression of adipose triglyceride lipase enhances tumor necrosis factor alpha-induced intercellular adhesion molecule-1 expression in human aortic endothelial cells via protein kinase C-dependent activation of nuclear factor-kappaB. J Biol Chem 2011, 286(37):32045-32053.
30. Sharma S., Adrogue J.V., Golfman L., et al. Intramyocardial lipid accumulation in the failing human heart resembles the lipotoxic rat heart. FASEB J 2004, 18(14):1692-1700.
31. Hirano K. A novel clinical entity: triglyceride deposit cardiomyovasculopathy. J Atheroscler Thromb 2009, 16(5):702-705.
32. Bergman R.N., Ader M. Free fatty acids and pathogenesis of type 2 diabetes mellitus. Trends Endocrinol Metab 2000, 11(9):351-356.
33. Kahn S.E., Hull R.L., Utzschneider K.M. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 2006, 444(7121):840-846.
34. Patti M.E., Butte A.J., Crunkhorn S., et al. Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: potential role of PGC1 and NRF1. Proc Natl Acad Sci U S A 2003, 100(14):8466-8471.
35. Boden G., Chen X., Ruiz J., et al. Mechanisms of fatty acid-induced inhibition of glucose uptake. J Clin Invest 1994, 93(6):2438-2446.
36. Staehr P., Hother-Nielsen O., Landau B.R., et al. Effects of free fatty acids per se on glucose production, gluconeogenesis, and glycogenolysis. Diabetes 2003, 52(2):260-267.
37. Kruszynska Y.T., Mulford M.I., Yu J.G., et al. Effects of nonesterified fatty acids on glucose metabolism after glucose ingestion. Diabetes 1997, 46(10):1586-1593.
38. Steinberg H.O., Paradisi G., Hook G., et al. Free fatty acid elevation impairs insulin-mediated vasodilation and nitric oxide production. Diabetes 2000, 49(7):1231-1238.
39. Steinberg H.O., Tarshoby M., Monestel R., et al. Elevated circulating free fatty acid levels impair endothelium-dependent vasodilation. J Clin Invest 1997, 100(5):1230-1239.
40. Kumar S., Durrington P.N., Bhatnagar D., et al. Suppression of non-esterified fatty acids to treat type A insulin resistance syndrome. Lancet 1994, 343(8905):1073-1074.
41. de Jongh R.T., Serne E.H., Ijzerman R.G., et al. Free fatty acid levels modulate microvascular function: relevance for obesity-associated insulin resistance, hypertension, and microangiopathy. Diabetes 2004, 53(11):2873-2882.
42. Pilz S., Scharnagl H., Tiran B., et al. Free fatty acids are independently associated with all-cause and cardiovascular mortality in subjects with coronary artery disease. J Clin Endocrinol Metab 2006, 91(7):2542-2547.
43. Il'yasova D., Wang F., D'Agostino R.B., et al. Prospective association between fasting NEFA and type 2 diabetes: impact of post-load glucose. Diabetologia 2010, 53(5):866-874.
44. Byrne C.D., Maison P., Halsall D., et al. Cross-sectional but not longitudinal associations between non-esterified fatty acid levels and glucose intolerance and other features of the metabolic syndrome. Diabet Med 1999, 16(12):1007-1015.
45. Karpe F., Dickmann J.R., Frayn K.N. Fatty acids, obesity, and insulin resistance: time for a reevaluation. Diabetes 2011, 60(10):2441-2449.
46. Opie L.H., Walfish P.G. Plasma free fatty acid concentrations in obesity. N Engl J Med 1963, 268:757-760.
47. Fielding B.A., Callow J., Owen R.M., et al. Postprandial lipemia: the origin of an early peak studied by specific dietary fatty acid intake during sequential meals. Am J Clin Nutr 1996, 63(1):36-41.
48. McQuaid S.E., Hodson L., Neville M.J., et al. Downregulation of adipose tissue fatty acid trafficking in obesity: a driver for ectopic fat deposition?. Diabetes 2011, 60(1):47-55.
49. Halcox J.P., Donald A.E., Ellins E., et al. Endothelial function predicts progression of carotid intima-media thickness. Circulation 2009, 119(7):1005-1012.
50. Steinberg H.O., Bayazeed B., Hook G., et al. Endothelial dysfunction is associated with cholesterol levels in the high normal range in humans. Circulation 1997, 96(10):3287-3293.
51. Feron O., Dessy C., Moniotte S., et al. Hypercholesterolemia decreases nitric oxide production by promoting the interaction of caveolin and endothelial nitric oxide synthase. J Clin Invest 1999, 103(6):897-905.
52. Duvillard L., Pont F., Florentin E., et al. Metabolic abnormalities of apolipoprotein B-containing lipoproteins in non-insulin-dependent diabetes: a stable isotope kinetic study. Eur J Clin Invest 2000, 30(8):685-694.
53. Verges B., Florentin E., Baillot-Rudoni S., et al. Effects of 20 mg rosuvastatin on VLDL1-, VLDL2-, IDL- and LDL-ApoB kinetics in type 2 diabetes. Diabetologia 2008, 51(8):1382-1390.
54. Koh K.K., Quon M.J., Han S.H., et al. Simvastatin improves flow-mediated dilation but reduces adiponectin levels and insulin sensitivity in hypercholesterolemic patients. Diabetes Care 2008, 31(4):776-782.
55. Adnitt P.I., Frayn K.N. Effects of metformin on glucose uptake by the isolated rat diaphragm. Br J Pharmacol 1972, 45(1):152P-153P.
56. Blair A., Shaul P.W., Yuhanna I.S., et al. Oxidized low density lipoprotein displaces endothelial nitric-oxide synthase (eNOS) from plasmalemmal caveolae and impairs eNOS activation. J Biol Chem 1999, 274(45):32512-32519.
57. Uittenbogaard A., Shaul P.W., Yuhanna I.S., et al. High density lipoprotein prevents oxidized low density lipoprotein-induced inhibition of endothelial nitric-oxide synthase localization and activation in caveolae. J Biol Chem 2000, 275(15):11278-11283.
58. Kita T., Yokode M., Ishii K., et al. The role of oxidized lipoproteins in the pathogenesis of atherosclerosis. Clin Exp Pharmacol Physiol Suppl 1992, 20:37-42.
59. Maor I., Aviram M. Oxidized low density lipoprotein leads to macrophage accumulation of unesterified cholesterol as a result of lysosomal trapping of the lipoprotein hydrolyzed cholesteryl ester. J Lipid Res 1994, 35(5):803-819.
60. Verges B., Brun J.M., Vaillant G., et al. Influence of obesity and hypertriglyceridaemia on the low HDL2-cholesterol level and on its relationship with prevalence of atherosclerosis in type 2 diabetes. Diabete Metab 1992, 18(4):289-297.
61. Golay A., Zech L., Shi M.Z., et al. High density lipoprotein (HDL) metabolism in noninsulin-dependent diabetes mellitus: measurement of HDL turnover using tritiated HDL. J Clin Endocrinol Metab 1987, 65(3):512-518.
62. Duvillard L., Pont F., Florentin E., et al. Inefficiency of insulin therapy to correct apolipoprotein A-I metabolic abnormalities in non-insulin-dependent diabetes mellitus. Atherosclerosis 2000, 152(1):229-237.
63. Besler C., Heinrich K., Rohrer L., et al. Mechanisms underlying adverse effects of HDL on eNOS-activating pathways in patients with coronary artery disease. J Clin Invest 2011, 121(7):2693-2708.
64. Persegol L., Verges B., Foissac M., et al. Inability of HDL from type 2 diabetic patients to counteract the inhibitory effect of oxidised LDL on endothelium-dependent vasorelaxation. Diabetologia 2006, 49(6):1380-1386.
65. Abel E.D., Litwin S.E., Sweeney G. Cardiac remodeling in obesity. Physiol Rev 2008, 88(2):389-419.
66. Lopaschuk G.D., Folmes C.D., Stanley W.C. Cardiac energy metabolism in obesity. Circ Res 2007, 101(4):335-347.
67. Hall J.E., da Silva A.A., do Carmo J.M., et al. Obesity-induced hypertension: role of sympathetic nervous system, leptin, and melanocortins. J Biol Chem 2010, 285(23):17271-17276.
68. Kenchaiah S., Evans J.C., Levy D., et al. Obesity and the risk of heart failure. N Engl J Med 2002, 347(5):305-313.
69. Dyntar D., Eppenberger-Eberhardt M., Maedler K., et al. Glucose and palmitic acid induce degeneration of myofibrils and modulate apoptosis in rat adult cardiomyocytes. Diabetes 2001, 50(9):2105-2113.
70. Park T.S., Hu Y., Noh H.L., et al. Ceramide is a cardiotoxin in lipotoxic cardiomyopathy. J Lipid Res 2008, 49(10):2101-2112.
71. Chess D.J., Lei B., Hoit B.D., et al. Effects of a high saturated fat diet on cardiac hypertrophy and dysfunction in response to pressure overload. J Diabet Complications 2008, 14(1):82-88.
72. Galvao T.F., Brown B.H., Hecker P.A., et al. High intake of saturated fat, but not polyunsaturated fat, improves survival in heart failure despite persistent mitochondrial defects. Cardiovasc Res 2012, 93(1):24-32.
73. Okere I.C., Chandler M.P., McElfresh T.A., et al. Differential effects of saturated and unsaturated fatty acid diets on cardiomyocyte apoptosis, adipose distribution, and serum leptin. Am J Physiol Heart Circ Physiol 2006, 291(1):H38-H44.
74. Okere I.C., Chess D.J., McElfresh T.A., et al. High-fat diet prevents cardiac hypertrophy and improves contractile function in the hypertensive dahl salt-sensitive rat. Clin Exp Pharmacol Physiol 2005, 32(10):825-831.
75. Stanley W.C., Dabkowski E.R., Ribeiro R.F., et al. Dietary fat and heart failure: moving from lipotoxicity to lipoprotection. Circ Res 2012, 110(5):764-776.
76. Halton T.L., Willett W.C., Liu S., et al. Low-carbohydrate-diet score and the risk of coronary heart disease in women. N Engl J Med 2006, 355(19):1991-2002.
77. Hu F.B., Willett W.C. Optimal diets for prevention of coronary heart disease. JAMA 2002, 288(20):2569-2578.
78. Lavie C.J., Milani R.V., Mehra M.R., et al. Omega-3 polyunsaturated fatty acids and cardiovascular diseases. J Am Coll Cardiol 2009, 54(7):585-594.
79. Mozaffarian D., Wu J.H. Omega-3 fatty acids and cardiovascular disease: effects on risk factors, molecular pathways, and clinical events. J Am Coll Cardiol 2011, 58(20):2047-2067.
80. Foley R. Cardiac disease in diabetic patients with renal disease. Acta Diabetol 2002, 39(Suppl 1):S9-S14.
81. Mogensen C.E., Christensen C.K., Vittinghus E. The stages in diabetic renal disease. With emphasis on the stage of incipient diabetic nephropathy. Diabetes 1983, 32(Suppl 2):64-78.
82. Stam F., van Guldener C., Becker A., et al. Endothelial dysfunction contributes to renal function-associated cardiovascular mortality in a population with mild renal insufficiency: the Hoorn study. J Am Soc Nephrol 2006, 17(2):537-545.
83. Stehouwer C.D. Endothelial dysfunction in diabetic nephropathy: state of the art and potential significance for non-diabetic renal disease. Nephrol Dial Transplant 2004, 19(4):778-781.
84. Attia D.M., Ni Z.N., Boer P., et al. Proteinuria is preceded by decreased nitric oxide synthesis and prevented by a NO donor in cholesterol-fed rats. Kidney Int 2002, 61(5):1776-1787.
85. Vaziri N.D., Moradi H. Mechanisms of dyslipidemia of chronic renal failure. Hemodial Int 2006, 10(1):1-7.
86. Vaziri N.D. Dyslipidemia of chronic renal failure: the nature, mechanisms, and potential consequences. Am J Physiol Renal Physiol 2006, 290(2):F262-F272.
87. Kronenberg F., Kuen E., Ritz E., et al. Lipoprotein(a) serum concentrations and apolipoprotein(a) phenotypes in mild and moderate renal failure. J Am Soc Nephrol 2000, 11(1):105-115.
88. Prinsen B.H., de Sain-van der Velden M.G., de Koning E.J., et al. Hypertriglyceridemia in patients with chronic renal failure: possible mechanisms. Kidney Int Suppl 2003, (84):S121-S124.
89. Dalrymple L.S., Kaysen G.A. The effect of lipoproteins on the development and progression of renal disease. Am J Nephrol 2008, 28(5):723-731.
90. Baines R.J., Brunskill N.J. Tubular toxicity of proteinuria. Nat Rev Nephrol 2011, 7(3):177-180.
91. Iacobini C., Menini S., Ricci C., et al. Advanced lipoxidation end-products mediate lipid-induced glomerular injury: role of receptor-mediated mechanisms. J Pathol 2009, 218(3):360-369.
92. Nosadini R., Tonolo G. Role of oxidized low density lipoproteins and free fatty acids in the pathogenesis of glomerulopathy and tubulointerstitial lesions in type 2 diabetes. Nutr Metab Cardiovasc Dis 2011, 21(2):79-85.
93. Obrosova I.G. Diabetic painful and insensate neuropathy: pathogenesis and potential treatments. Neurotherapeutics 2009, 6(4):638-647.
94. Andersen H. Motor dysfunction in diabetes. Diabetes Metab Res Rev 2012, 28(Suppl 1):89-92.
95. Said G., Baudoin D., Toyooka K. Sensory loss, pains, motor deficit and axonal regeneration in length-dependent diabetic polyneuropathy. J Neurol 2008, 255(11):1693-1702.
96. Cameron N.E., Cotter M.A. Diabetes causes an early reduction in autonomic ganglion blood flow in rats. J Diabet Complications 2001, 15(4):198-202.
97. Zent R., Pozzi A. Angiogenesis in diabetic nephropathy. Semin Nephrol 2007, 27(2):161-171.
98. Tesfaye S., Chaturvedi N., Eaton S.E., et al. Vascular risk factors and diabetic neuropathy. N Engl J Med 2005, 352(4):341-350.
99. Witte D.R., Tesfaye S., Chaturvedi N., et al. Risk factors for cardiac autonomic neuropathy in type 1 diabetes mellitus. Diabetologia 2005, 48(1):164-171.
100. Lacigova S., Bartunek L., Cechurova D., et al. Influence of cardiovascular autonomic neuropathy on atherogenesis and heart function in patients with type 1 diabetes. Diabetes Res Clin Pract 2009, 83(1):26-31.
101. Obrosova I.G., Ilnytska O., Lyzogubov V.V., et al. High-fat diet induced neuropathy of pre-diabetes and obesity: effects of "healthy" diet and aldose reductase inhibition. Diabetes 2007, 56(10):2598-2608.
102. Padilla A., Descorbeth M., Almeyda A.L., et al. Hyperglycemia magnifies Schwann cell dysfunction and cell death triggered by PA-induced lipotoxicity. Brain Res 2011, 1370:64-79.
103. Nowicki M., Muller K., Serke H., et al. Oxidized low-density lipoprotein (oxLDL)-induced cell death in dorsal root ganglion cell cultures depends not on the lectin-like oxLDL receptor-1 but on the toll-like receptor-4. J Neurosci Res 2010, 88(2):403-412.
104. Yan S.S., Chen D., Yan S., et al. RAGE is a key cellular target for Abeta-induced perturbation in Alzheimer's disease. Front Biosci 2012, 4:240-250.
105. Johannsen D.L., Ravussin E. Can increased muscle ROS scavenging keep older animals young and metabolically fit?. Cell Metab 2010, 12(6):557-558.
106. Preedy V.R., Adachi J., Asano M., et al. Free radicals in alcoholic myopathy: indices of damage and preventive studies. Free Radic Biol Med 2002, 32(8):683-687.
107. Victor V.M., Rocha M., Herance R., et al. Oxidative stress and mitochondrial dysfunction in type 2 diabetes. Curr Pharm Des 2011, 17(36):3947-3958.
108. Hayek T., Kaplan M., Kerry R., et al. Macrophage NADPH oxidase activation, impaired cholesterol fluxes, and increased cholesterol biosynthesis in diabetic mice: a stimulatory role for D-glucose. Atherosclerosis 2007, 195(2):277-286.
109. Maloney E., Sweet I.R., Hockenbery D.M., et al. Activation of NF-kappaB by palmitate in endothelial cells: a key role for NADPH oxidase-derived superoxide in response to TLR4 activation. Arterioscler Thromb Vasc Biol 2009, 29(9):1370-1375.
110. Steinbeck M.J., Robinson J.M., Karnovsky M.J. Activation of the neutrophil NADPH-oxidase by free fatty acids requires the ionized carboxyl group and partitioning into membrane lipid. J Leukoc Biol 1991, 49(4):360-368.
111. Chinen I., Shimabukuro M., Yamakawa K., et al. Vascular lipotoxicity: endothelial dysfunction via fatty-acid-induced reactive oxygen species overproduction in obese Zucker diabetic fatty rats. Endocrinology 2007, 148(1):160-165.
112. Curnutte J.T., Erickson R.W., Ding J., et al. Reciprocal interactions between protein kinase C and components of the NADPH oxidase complex may regulate superoxide production by neutrophils stimulated with a phorbol ester. J Biol Chem 1994, 269(14):10813-10819.
113. Nauseef W.M., Volpp B.D., McCormick S., et al. Assembly of the neutrophil respiratory burst oxidase. Protein kinase C promotes cytoskeletal and membrane association of cytosolic oxidase components. J Biol Chem 1991, 266(9):5911-5917.
114. Hulsmans M., Van Dooren E., Holvoet P. Mitochondrial reactive oxygen species and risk of atherosclerosis. Curr Atheroscler Rep 2012, 14(3):264-276.
115. Schonfeld P., Wojtczak L. Fatty acids as modulators of the cellular production of reactive oxygen species. Free Radic Biol Med 2008, 45(3):231-241.
116. Rocha M., Apostolova N., Hernandez-Mijares A., et al. Oxidative stress and endothelial dysfunction in cardiovascular disease: mitochondria-targeted therapeutics. Curr Med Chem 2010, 17(32):3827-3841.
117. Kim J.A., Wei Y., Sowers J.R. Role of mitochondrial dysfunction in insulin resistance. Circ Res 2008, 102(4):401-414.
118. Moukdar F., Robidoux J., Lyght O., et al. Reduced antioxidant capacity and diet-induced atherosclerosis in uncoupling protein-2-deficient mice. J Lipid Res 2009, 50(1):59-70.
119. Erdei N., Toth A., Pasztor E.T., et al. High-fat diet-induced reduction in nitric oxide-dependent arteriolar dilation in rats: role of xanthine oxidase-derived superoxide anion. Am J Physiol Heart Circ Physiol 2006, 291(5):H2107-H2115.
120. Pannirselvam M., Verma S., Anderson T.J., et al. Cellular basis of endothelial dysfunction in small mesenteric arteries from spontaneously diabetic (db/db -/-) mice: role of decreased tetrahydrobiopterin bioavailability. Br J Pharmacol 2002, 136(2):255-263.
121. Vasquez-Vivar J., Kalyanaraman B., Martasek P. The role of tetrahydrobiopterin in superoxide generation from eNOS: enzymology and physiological implications. Free Radic Res 2003, 37(2):121-127.
122. Wellen K.E., Hotamisligil G.S. Obesity-induced inflammatory changes in adipose tissue. J Clin Invest 2003, 112(12):1785-1788.
123. Xu H., Barnes G.T., Yang Q., et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 2003, 112(12):1821-1830.
124. Linton M.F., Fazio S. Macrophages, inflammation, and atherosclerosis. Int J Obes Relat Metab Disord 2003, 27(Suppl 3):S35-S40.
125. Kim F., Pham M., Luttrell I., et al. Toll-like receptor-4 mediates vascular inflammation and insulin resistance in diet-induced obesity. Circ Res 2007, 100(11):1589-1596.
126. Shi H., Kokoeva M.V., Inouye K., et al. TLR4 links innate immunity and fatty acid-induced insulin resistance. J Clin Invest 2006, 116(11):3015-3025.
127. Nguyen M.T., Favelyukis S., Nguyen A.K., et al. A subpopulation of macrophages infiltrates hypertrophic adipose tissue and is activated by free fatty acids via toll-like receptors 2 and 4 and JNK-dependent pathways. J Biol Chem 2007, 282(48):35279-35292.
128. Michelsen K.S., Doherty T.M., Shah P.K., et al. Role of Toll-like receptors in atherosclerosis. Circ Res 2004, 95(12):e96-e97.
129. Son J.W., Jang E.H., Kim M.K., et al. Serum BMP-4 levels in relation to arterial stiffness and carotid atherosclerosis in patients with Type 2 diabetes. Biomark Med 2011, 5(6):827-835.
130. Geng H., Wang A., Rong G., et al. The effects of ox-LDL in human atherosclerosis may be mediated in part via the toll-like receptor 4 pathway. Mol Cell Biochem 2010, 342(1-2):201-206.
131. Holland W.L., Bikman B.T., Wang L.P., et al. Lipid-induced insulin resistance mediated by the proinflammatory receptor TLR4 requires saturated fatty acid-induced ceramide biosynthesis in mice. J Clin Invest 2011, 121(5):1858-1870.
132. Montagnani M., Chen H., Barr V.A., et al. Insulin-stimulated activation of eNOS is independent of Ca2+ but requires phosphorylation by Akt at Ser(1179). J Biol Chem 2001, 276(32):30392-30398.
133. Montagnani M., Ravichandran L.V., Chen H., et al. Insulin receptor substrate-1 and phosphoinositide-dependent kinase-1 are required for insulin-stimulated production of nitric oxide in endothelial cells. Mol Endocrinol 2002, 16(8):1931-1942.
134. Gao Z., Hwang D., Bataille F., et al. Serine phosphorylation of insulin receptor substrate 1 by inhibitor kappa B kinase complex. J Biol Chem 2002, 277(50):48115-48121.
135. Lee S., Lynn E.G., Kim J.A., et al. Protein kinase C-zeta phosphorylates insulin receptor substrate-1, -3, and -4 but not -2: isoform specific determinants of specificity in insulin signaling. Endocrinology 2008, 149(5):2451-2458.
136. Steinberg H.O., Brechtel G., Johnson A., et al. Insulin-mediated skeletal muscle vasodilation is nitric oxide dependent. A novel action of insulin to increase nitric oxide release. J Clin Invest 1994, 94(3):1172-1179.
137. Bikman B.T., Summers S.A. Ceramides as modulators of cellular and whole-body metabolism. J Clin Invest 2011, 121(11):4222-4230.
138. Wilson-Fritch L., Burkart A., Bell G., et al. Mitochondrial biogenesis and remodeling during adipogenesis and in response to the insulin sensitizer rosiglitazone. Mol Cell Biol 2003, 23(3):1085-1094.
139. Bogacka I., Xie H., Bray G.A., et al. Pioglitazone induces mitochondrial biogenesis in human subcutaneous adipose tissue in vivo. Diabetes 2005, 54(5):1392-1399.
140. Nisoli E., Clementi E., Carruba M.O., et al. Defective mitochondrial biogenesis: a hallmark of the high cardiovascular risk in the metabolic syndrome?. Circ Res 2007, 100(6):795-806.
141. Le Gouill E., Jimenez M., Binnert C., et al. Endothelial nitric oxide synthase (eNOS) knockout mice have defective mitochondrial beta-oxidation. Diabetes 2007, 56(11):2690-2696.
142. Petersen K.F., Dufour S., Befroy D., et al. Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes. N Engl J Med 2004, 350(7):664-671.
143. Ozcan U., Cao Q., Yilmaz E., et al. Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science 2004, 306(5695):457-461.
144. Ozcan U., Yilmaz E., Ozcan L., et al. Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes. Science 2006, 313(5790):1137-1140.
145. Boden G., Duan X., Homko C., et al. Increase in endoplasmic reticulum stress-related proteins and genes in adipose tissue of obese, insulin-resistant individuals. Diabetes 2008, 57(9):2438-2444.
146. Kars M., Yang L., Gregor M.F., et al. Tauroursodeoxycholic acid may improve liver and muscle but not adipose tissue insulin sensitivity in obese men and women. Diabetes 2010, 59(8):1899-1905.
147. Hotamisligil G.S. Inflammation and endoplasmic reticulum stress in obesity and diabetes. Int J Obes(Lond) 2008, 32(Suppl 7):S52-S54.
148. Vladykovskaya E., Sithu S.D., Haberzettl P., et al. The lipid peroxidation product, 4-hydroxy-trans-2-nonenal causes endothelial activation by inducing endoplasmic reticulum stress. J Biol Chem 2012 Jan 6, [Epub ahead of print].
149. Zhang Y., Xue R., Zhang Z., et al. Palmitic and linoleic acids induce ER stress and apoptosis in hepatoma cells. Lipids Health Dis 2012, 11:1.
150. Fu S., Yang L., Li P., et al. Aberrant lipid metabolism disrupts calcium homeostasis causing liver endoplasmic reticulum stress in obesity. Nature 2011, 473(7348):528-531.
151. Tabas I. The role of endoplasmic reticulum stress in the progression of atherosclerosis. Circ Res 2010, 107(7):839-850.
152. Ji C., Kaplowitz N. ER stress: can the liver cope?. J Hepatol 2006, 45(2):321-333.
153. Gregor M.F., Yang L., Fabbrini E., et al. Endoplasmic reticulum stress is reduced in tissues of obese subjects after weight loss. Diabetes 2009, 58(3):693-700.
154. Aguirre V., Uchida T., Yenush L., et al. The c-Jun NH(2)-terminal kinase promotes insulin resistance during association with insulin receptor substrate-1 and phosphorylation of Ser(307). J Biol Chem 2000, 275(12):9047-9054.
155. Carlson C.J., White M.F., Rondinone C.M. Mammalian target of rapamycin regulates IRS-1 serine 307 phosphorylation. Biochem Biophys Res Commun 2004, 316(2):533-539.
156. Hilder T.L., Tou J.C., Grindeland R.E., et al. Phosphorylation of insulin receptor substrate-1 serine 307 correlates with JNK activity in atrophic skeletal muscle. FEBS Lett 2003, 553(1-2):63-67.
157. Chun L., Junlin Z., Aimin W., et al. Inhibition of ceramide synthesis reverses endothelial dysfunction and atherosclerosis in streptozotocin-induced diabetic rats. Diabetes Res Clin Pract 2011, 93(1):77-85.
158. Datta S.R., Dudek H., Tao X., et al. Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell 1997, 91(2):231-241.
159. Zhou H., Summers S.A., Birnbaum M.J., et al. Inhibition of Akt kinase by cell-permeable ceramide and its implications for ceramide-induced apoptosis. J Biol Chem 1998, 273(26):16568-16575.
160. Katsuyama K., Shichiri M., Marumo F., et al. Role of nuclear factor-kappaB activation in cytokine- and sphingomyelinase-stimulated inducible nitric oxide synthase gene expression in vascular smooth muscle cells. Endocrinology 1998, 139(11):4506-4512.
161. Pahan K., Sheikh F.G., Khan M., et al. Sphingomyelinase and ceramide stimulate the expression of inducible nitric-oxide synthase in rat primary astrocytes. J Biol Chem 1998, 273(5):2591-2600.
162. Dimmeler S., Haendeler J., Galle J., et al. Oxidized low-density lipoprotein induces apoptosis of human endothelial cells by activation of CPP32-like proteases. A mechanistic clue to the 'response to injury' hypothesis. Circulation 1997, 95(7):1760-1763.
163. Suc I., Escargueil-Blanc I., Troly M., et al. HDL and ApoA prevent cell death of endothelial cells induced by oxidized LDL. Arterioscler Thromb Vasc Biol 1997, 17(10):2158-2166.
164. Noor R., Shuaib U., Wang C.X., et al. High-density lipoprotein cholesterol regulates endothelial progenitor cells by increasing eNOS and preventing apoptosis. Atherosclerosis 2007, 192(1):92-99.
165. Hoffmann J., Haendeler J., Aicher A., et al. Aging enhances the sensitivity of endothelial cells toward apoptotic stimuli: important role of nitric oxide. Circ Res 2001, 89(8):709-715.
166. Barlow C.E., LaMonte M.J., Fitzgerald S.J., et al. Cardiorespiratory fitness is an independent predictor of hypertension incidence among initially normotensive healthy women. Am J Epidemiol 2006, 163(2):142-150.
167. Sui X., LaMonte M.J., Laditka J.N., et al. Cardiorespiratory fitness and adiposity as mortality predictors in older adults. JAMA 2007, 298(21):2507-2516.
168. Carter S.L., Rennie C., Tarnopolsky M.A. Substrate utilization during endurance exercise in men and women after endurance training. Am J Physiol Endocrinol Metab 2001, 280(6):E898-E907.
169. Schrauwen P., van Aggel-Leijssen D.P., Hul G., et al. The effect of a 3-month low-intensity endurance training program on fat oxidation and acetyl-CoA carboxylase-2 expression. Diabetes 2002, 51(7):2220-2226.
170. Liu L., Shi X., Bharadwaj K.G., et al. DGAT1 expression increases heart triglyceride content but ameliorates lipotoxicity. J Biol Chem 2009, 284(52):36312-36323.
171. Criswell D., Powers S., Dodd S., et al. High intensity training-induced changes in skeletal muscle antioxidant enzyme activity. Med Sci Sports Exerc 1993, 25(10):1135-1140.
172. Pinto A., Di Raimondo D., Tuttolomondo A., et al. Effects of physical exercise on inflammatory markers of atherosclerosis. Curr Pharm Des 2012, 287(14):11398-11409.
173. Menshikova E.V., Ritov V.B., Ferrell R.E., et al. Characteristics of skeletal muscle mitochondrial biogenesis induced by moderate-intensity exercise and weight loss in obesity. J Appl Phys 2007, 103(1):21-27.
174. Richter E.A., Ruderman N.B. AMPK and the biochemistry of exercise: implications for human health and disease. Biochem J 2009, 418(2):261-275.
175. Ropelle E.R., Flores M.B., Cintra D.E., et al. IL-6 and IL-10 anti-inflammatory activity links exercise to hypothalamic insulin and leptin sensitivity through IKKbeta and ER stress inhibition. PLoS Biol 2010, 8(8):e1000465.
176. Christ-Roberts C.Y., Pratipanawatr T., Pratipanawatr W., et al. Exercise training increases glycogen synthase activity and GLUT4 expression but not insulin signaling in overweight nondiabetic and type 2 diabetic subjects. Metabolism 2004, 53(9):1233-1242.
177. Maiorana A., O'Driscoll G., Taylor R., et al. Exercise and the nitric oxide vasodilator system. Sports Med 2003, 33(14):1013-1035.
178. Colberg S.R., Albright A.L., Blissmer B.J., et al. Exercise and Type 2 Diabetes. Med Sci Sports Exerc 2010 Dec, 42(12):2283-2303.
179. Lim S., Despres J.P., Koh K.K. Prevention of atherosclerosis in overweight/obese patients. - In need of novel multi-targeted approaches. Circ J 2011, 75(5):1019-1027.
180. Istvan E.S., Deisenhofer J. Structural mechanism for statin inhibition of HMG-CoA reductase. Science 2001, 292(5519):1160-1164.
181. Group H.P.S.C. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002, 360(9326):7-22.
182. Ridker P.M., Cannon C.P., Morrow D., et al. C-reactive protein levels and outcomes after statin therapy. N Engl J Med 2005, 352(1):20-28.
183. Ridker P.M., Danielson E., Fonseca F.A., et al. Reduction in C-reactive protein and LDL cholesterol and cardiovascular event rates after initiation of rosuvastatin: a prospective study of the JUPITER trial. Lancet 2009, 373(9670):1175-1182.
184. Sorrentino S., Landmesser U. Nonlipid-lowering effects of statins. Curr Treat Options Cardiovasc Med 2005, 7(6):459-466.
185. Zhou Q., Liao J.K. Pleiotropic effects of statins. - Basic research and clinical perspectives. Circ J 2010, 74(5):818-826.
186. Wang C.Y., Liu P.Y., Liao J.K. Pleiotropic effects of statin therapy: molecular mechanisms and clinical results. Trends Mol Med 2008, 14(1):37-44.
187. Colhoun H.M., Betteridge D.J., Durrington P.N., et al. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet 2004, 364(9435):685-696.
188. Koh K.K., Quon M.J., Rosenson R.S., et al. Vascular and metabolic effects of treatment of combined hyperlipidemia: focus on statins and fibrates. Int J Cardiol 2008, 124(2):149-159.
189. Rawlings R., Nohria A., Liu P.Y., et al. Comparison of effects of rosuvastatin (10 mg) versus atorvastatin (40 mg) on rho kinase activity in caucasian men with a previous atherosclerotic event. Am J Cardiol 2009, 103(4):437-441.
190. Liu P.Y., Liu Y.W., Lin L.J., et al. Evidence for statin pleiotropy in humans: differential effects of statins and ezetimibe on rho-associated coiled-coil containing protein kinase activity, endothelial function, and inflammation. Circulation 2009, 119(1):131-138.
191. Gabay C., Kushner I. Acute-phase proteins and other systemic responses to inflammation. N Engl J Med 1999, 340(6):448-454.
192. Wang C.H., Li S.H., Weisel R.D., et al. C-reactive protein upregulates angiotensin type 1 receptors in vascular smooth muscle. Circulation 2003, 107(13):1783-1790.
193. Kleemann R., Verschuren L., de Rooij B.J., et al. Evidence for anti-inflammatory activity of statins and PPARalpha activators in human C-reactive protein transgenic mice in vivo and in cultured human hepatocytes in vitro. Blood 2004, 103(11):4188-4194.
194. Laufs U., La Fata V., Plutzky J., et al. Upregulation of endothelial nitric oxide synthase by HMG CoA reductase inhibitors. Circulation 1998, 97(12):1129-1135.
195. Laufs U., Liao J.K. Post-transcriptional regulation of endothelial nitric oxide synthase mRNA stability by Rho GTPase. J Biol Chem 1998, 273(37):24266-24271.
196. Kosmidou I., Moore J.P., Weber M., et al. Statin treatment and 3' polyadenylation of eNOS mRNA. Arterioscler Thromb Vasc Biol 2007, 27(12):2642-2649.
197. Wenzel P., Daiber A., Oelze M., et al. Mechanisms underlying recoupling of eNOS by HMG-CoA reductase inhibition in a rat model of streptozotocin-induced diabetes mellitus. Atherosclerosis 2008, 198(1):65-76.
198. Antoniades C., Bakogiannis C., Leeson P., et al. Rapid, direct effects of statin treatment on arterial redox state and nitric oxide bioavailability in human atherosclerosis via tetrahydrobiopterin-mediated endothelial nitric oxide synthase coupling. Circulation 2011, 124(3):335-345.
199. Hattori Y., Nakanishi N., Akimoto K., et al. HMG-CoA reductase inhibitor increases GTP cyclohydrolase I mRNA and tetrahydrobiopterin in vascular endothelial cells. Arterioscler Thromb Vasc Biol 2003, 23(2):176-182.
200. Rueckschloss U., Galle J., Holtz J., et al. Induction of NAD(P)H oxidase by oxidized low-density lipoprotein in human endothelial cells: antioxidative potential of hydroxymethylglutaryl coenzyme A reductase inhibitor therapy. Circulation 2001, 104(15):1767-1772.
201. Mason R.P., Kubant R., Heeba G., et al. Synergistic effect of amlodipine and atorvastatin in reversing LDL-induced endothelial dysfunction. Pharm Res 2008, 25(8):1798-1806.
202. Otto A., Fontaine J., Tschirhart E., et al. Rosuvastatin treatment protects against nitrate-induced oxidative stress in eNOS knockout mice: implication of the NAD(P)H oxidase pathway. Br J Pharmacol 2006, 148(4):544-552.
203. Cangemi R., Loffredo L., Carnevale R., et al. Early decrease of oxidative stress by atorvastatin in hypercholesterolaemic patients: effect on circulating vitamin E. Eur Heart J 2008, 29(1):54-62.
204. Morawietz H., Erbs S., Holtz J., et al. Endothelial protection, AT1 blockade and cholesterol-dependent oxidative stress: the EPAS trial. Circulation 2006, 114(Suppl 1):I296-I301.
205. Nickenig G., Baumer A.T., Temur Y., et al. Statin-sensitive dysregulated AT1 receptor function and density in hypercholesterolemic men. Circulation 1999, 100(21):2131-2134.
206. Plutzky J. The PPAR-RXR transcriptional complex in the vasculature: energy in the balance. Circ Res 2011, 108(8):1002-1016.
207. Yki-Jarvinen H. Thiazolidinediones. N Engl J Med 2004, 351(11):1106-1118.
208. Friedland S.N., Leong A., Filion K.B., et al. The cardiovascular effects of peroxisome proliferator-activated receptor agonists. Am J Med 2012, 125(2):126-133.
209. Willson T.M., Brown P.J., Sternbach D.D., et al. The PPARs: from orphan receptors to drug discovery. J Med Chem 2000, 43(4):527-550.
210. Marx N., Sukhova G.K., Collins T., et al. PPARalpha activators inhibit cytokine-induced vascular cell adhesion molecule-1 expression in human endothelial cells. Circulation 1999, 99(24):3125-3131.
211. Ziouzenkova O., Perrey S., Asatryan L., et al. Lipolysis of triglyceride-rich lipoproteins generates PPAR ligands: evidence for an antiinflammatory role for lipoprotein lipase. Acad Sci U S A 2003, 100(5):2730-2735.
212. Marx N., Mackman N., Schonbeck U., et al. PPARalpha activators inhibit tissue factor expression and activity in human monocytes. Circulation 2001, 103(2):213-219.
213. Muhlestein J.B., May H.T., Jensen J.R., et al. The reduction of inflammatory biomarkers by statin, fibrate, and combination therapy among diabetic patients with mixed dyslipidemia: the DIACOR (Diabetes and Combined Lipid Therapy Regimen) study. J Am Coll Cardiol 2006, 48(2):396-401.
214. Rigamonti E., Chinetti-Gbaguidi G., Staels B. Regulation of macrophage functions by PPAR-alpha, PPAR-gamma, and LXRs in mice and men. Arterioscler Thromb Vasc Biol 2008, 28(6):1050-1059.
215. Babaev V.R., Ishiguro H., Ding L., et al. Macrophage expression of peroxisome proliferator-activated receptor-alpha reduces atherosclerosis in low-density lipoprotein receptor-deficient mice. Circulation 2007, 116(12):1404-1412.
216. Diep Q.N., Amiri F., Touyz R.M., et al. PPARalpha activator effects on Ang II-induced vascular oxidative stress and inflammation. Hypertension 2002, 40(6):866-871.
217. Koh K.K., Han S.H., Quon M.J., et al. Beneficial effects of fenofibrate to improve endothelial dysfunction and raise adiponectin levels in patients with primary hypertriglyceridemia. Diabetes Care 2005, 28(6):1419-1424.
218. Rubins H.B., Robins S.J., Collins D., et al. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. N Engl J Med 1999, 341(6):410-418.
219. Rubins H.B., Robins S.J., Collins D., et al. Diabetes, plasma insulin, and cardiovascular disease: subgroup analysis from the Department of Veterans Affairs high-density lipoprotein intervention trial (VA-HIT). Arch Intern Med 2002, 162(22):2597-2604.
220. Keech A., Simes R.J., Barter P., et al. Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Lancet 2005, 366(9500):1849-1861.
221. Ginsberg H.N., Elam M.B., Lovato L.C., et al. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med 2010, 362(17):1563-1574.
222. Elam M., Lovato L.C., Ginsberg H. Role of fibrates in cardiovascular disease prevention, the ACCORD-Lipid perspective. Curr Opin Lipidol 2010, 22(1):55-61.
223. Miyazaki Y., Glass L., Triplitt C., et al. Effect of rosiglitazone on glucose and non-esterified fatty acid metabolism in Type II diabetic patients. Diabetologia 2001, 44(12):2210-2219.
224. Miyazaki Y., Mahankali A., Matsuda M., et al. Effect of pioglitazone on abdominal fat distribution and insulin sensitivity in type 2 diabetic patients. J Clin Endocrinol Metab 2002, 87(6):2784-2791.
225. Miyazaki Y., He H., Mandarino L.J., et al. Rosiglitazone improves downstream insulin receptor signaling in type 2 diabetic patients. Diabetes 2003, 52(8):1943-1950.
226. Bajaj M., Baig R., Suraamornkul S., et al. Effects of pioglitazone on intramyocellular fat metabolism in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab 2010, 95(4):1916-1923.
227. Bays H., Mandarino L., DeFronzo R.A. Role of the adipocyte, free fatty acids, and ectopic fat in pathogenesis of type 2 diabetes mellitus: peroxisomal proliferator-activated receptor agonists provide a rational therapeutic approach. J Clin Endocrinol Metab 2004, 89(2):463-478.
228. Kubota N., Terauchi Y., Yamauchi T., et al. Disruption of adiponectin causes insulin resistance and neointimal formation. J Biol Chem 2002, 277(29):25863-25866.
229. Yamauchi T., Kadowaki T. Physiological and pathophysiological roles of adiponectin and adiponectin receptors in the integrated regulation of metabolic and cardiovascular diseases. Int J Obes(Lond) 2008, 32(Suppl 7):S13-S18.
230. Puigserver P., Spiegelman B.M. Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha): transcriptional coactivator and metabolic regulator. Endocr Rev 2003, 24(1):78-90.
231. Coletta D.K., Sriwijitkamol A., Wajcberg E., et al. Pioglitazone stimulates AMP-activated protein kinase signalling and increases the expression of genes involved in adiponectin signalling, mitochondrial function and fat oxidation in human skeletal muscle in vivo: a randomised trial. Diabetologia 2009, 52(4):723-732.
232. Brown J.D., Plutzky J. Peroxisome proliferator-activated receptors as transcriptional nodal points and therapeutic targets. Circulation 2007, 115(4):518-533.
233. Calnek D.S., Mazzella L., Roser S., et al. Peroxisome proliferator-activated receptor gamma ligands increase release of nitric oxide from endothelial cells. Arterioscler Thromb Vasc Biol 2003, 23(1):52-57.
234. Chen N.G., Sarabia S.F., Malloy P.J., et al. PPARgamma agonists enhance human vascular endothelial adhesiveness by increasing ICAM-1 expression. Biochem Biophys Res Commun 1999, 263(3):718-722.
235. Marx N., Mach F., Sauty A., et al. Peroxisome proliferator-activated receptor-gamma activators inhibit IFN-gamma-induced expression of the T cell-active CXC chemokines IP-10, Mig, and I-TAC in human endothelial cells. J Immunol 2000, 164(12):6503-6508.
236. Inoue I., Goto S., Matsunaga T., et al. The ligands/activators for peroxisome proliferator-activated receptor alpha (PPARalpha) and PPARgamma increase Cu2+, Zn2+-superoxide dismutase and decrease p22phox message expressions in primary endothelial cells. Metabolism 2001, 50(1):3-11.
237. Delerive P., Martin-Nizard F., Chinetti G., et al. Peroxisome proliferator-activated receptor activators inhibit thrombin-induced endothelin-1 production in human vascular endothelial cells by inhibiting the activator protein-1 signaling pathway. Circ Res 1999, 85(5):394-402.
238. Satoh H., Tsukamoto K., Hashimoto Y., et al. Thiazolidinediones suppress endothelin-1 secretion from bovine vascular endothelial cells: a new possible role of PPARgamma on vascular endothelial function. Biochem Biophys Res Commun 1999, 254(3):757-763.
239. Sugawara A., Takeuchi K., Uruno A., et al. Transcriptional suppression of type 1 angiotensin II receptor gene expression by peroxisome proliferator-activated receptor-gamma in vascular smooth muscle cells. Endocrinology 2001, 142(7):3125-3134.
240. Dormandy J.A., Charbonnel B., Eckland D.J., et al. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet 2005, 366(9493):1279-1289.
241. Nissen S.E., Nicholls S.J., Wolski K., et al. Comparison of pioglitazone vs glimepiride on progression of coronary atherosclerosis in patients with type 2 diabetes: the PERISCOPE randomized controlled trial. JAMA 2008, 299(13):1561-1573.
242. Mazzone T., Meyer P.M., Feinstein S.B., et al. Effect of pioglitazone compared with glimepiride on carotid intima-media thickness in type 2 diabetes: a randomized trial. JAMA 2006, 296(21):2572-2581.
243. Davidson M., Meyer P.M., Haffner S., et al. Increased high-density lipoprotein cholesterol predicts the pioglitazone-mediated reduction of carotid intima-media thickness progression in patients with type 2 diabetes mellitus. Circulation 2008, 117(16):2123-2130.
244. Nicholls S.J., Tuzcu E.M., Wolski K., et al. Lowering the triglyceride/high-density lipoprotein cholesterol ratio is associated with the beneficial impact of pioglitazone on progression of coronary atherosclerosis in diabetic patients: insights from the PERISCOPE (Pioglitazone Effect on Regression of Intravascular Sonographic Coronary Obstruction Prospective Evaluation) study. J Am Coll Cardiol 2011, 57(2):153-159.
245. Nissen S.E., Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med 2007, 356(24):2457-2471.
246. Simo R., Rodriguez A., Caveda E. Different effects of thiazolidinediones on cardiovascular risk in patients with type 2 diabetes mellitus: pioglitazone versus rosiglitazone. Curr Drug Saf 2010, 5(3):234-244.
247. Sgarra L., Addabbo F., Potenza M.A., et al. Determinants of evolving cardiovascular benefit/risk profile of rosiglitazone during the natural history of diabetes. Am J Physiol Endocrinol Metab 2012, 302(10):E1171-E1182. [Epub 2012 Feb 28].
248. Goldberg R.B., Kendall D.M., Deeg M.A., et al. A comparison of lipid and glycemic effects of pioglitazone and rosiglitazone in patients with type 2 diabetes and dyslipidemia. Diabetes Care 2005, 28(7):1547-1554.
249. Balakumar P., Rose M., Ganti S.S., et al. PPAR dual agonists: are they opening Pandora's Box?. Pharm Res 2007, 56(2):91-98.
250. Tozzo E., Ponticiello R., Swartz J., et al. The dual peroxisome proliferator-activated receptor alpha/gamma activator muraglitazar prevents the natural progression of diabetes in db/db mice. J Pharmacol Exp Ther 2007, 321(1):107-115.
251. Kendall D.M., Rubin C.J., Mohideen P., et al. Improvement of glycemic control, triglycerides, and HDL cholesterol levels with muraglitazar, a dual (alpha/gamma) peroxisome proliferator-activated receptor activator, in patients with type 2 diabetes inadequately controlled with metformin monotherapy: A double-blind, randomized, pioglitazone-comparative study. Diabetes Care 2006, 29(5):1016-1023.
252. Chira E.C., McMillen T.S., Wang S., et al. Tesaglitazar, a dual peroxisome proliferator-activated receptor alpha/gamma agonist, reduces atherosclerosis in female low density lipoprotein receptor deficient mice. Atherosclerosis 2007, 195(1):100-109.
253. Liao J., Soltani Z., Ebenezer P., et al. Tesaglitazar, a dual peroxisome proliferator-activated receptor agonist (PPAR alpha/gamma), improves metabolic abnormalities and reduces renal injury in obese Zucker rats. Nephron Exp Nephrol 2009, 114(2):e61-e68.
254. Cha D.R., Zhang X., Zhang Y., et al. Peroxisome proliferator activated receptor alpha/gamma dual agonist tesaglitazar attenuates diabetic nephropathy in db/db mice. Diabetes 2007, 56(8):2036-2045.
255. Cox S.L. Tesaglitazar: a promising approach in type 2 diabetes. Drugs Today (Barc) 2006, 42(3):139-146.
256. Li P.P., Shan S., Chen Y.T., et al. The PPARalpha/gamma dual agonist chiglitazar improves insulin resistance and dyslipidemia in MSG obese rats. Br J Pharmacol 2006, 148(5):610-618.
257. Henry R.R., Lincoff A.M., Mudaliar S., et al. Effect of the dual peroxisome proliferator-activated receptor-alpha/gamma agonist aleglitazar on risk of cardiovascular disease in patients with type 2 diabetes (SYNCHRONY): a phase II, randomised, dose-ranging study. Lancet 2009, 374(9684):126-135.
258. Ferrario C.M., Richmond R.S., Smith R., et al. Renin-angiotensin system as a therapeutic target in managing atherosclerosis. Am J Ther 2004, 11(1):44-53.
259. Yusuf S., Gerstein H., Hoogwerf B., et al. Ramipril and the development of diabetes. JAMA 2001, 286(15):1882-1885.
260. Barzilay J.I., Davis B.R., Cutler J.A., et al. Fasting glucose levels and incident diabetes mellitus in older nondiabetic adults randomized to receive 3 different classes of antihypertensive treatment: a report from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Arch Intern Med 2006, 166(20):2191-2201.
261. Bosch J., Yusuf S., Gerstein H.C., et al. Effect of ramipril on the incidence of diabetes. N Engl J Med 2006, 355(15):1551-1562.
262. McMurray J.J., Holman R.R., Haffner S.M., et al. Effect of valsartan on the incidence of diabetes and cardiovascular events. N Engl J Med 2010, 362(16):1477-1490.
263. Van Linthout S., Spillmann F., Lorenz M., et al. Vascular-protective effects of high-density lipoprotein include the downregulation of the angiotensin II type 1 receptor. Hypertension 2009, 53(4):682-687.
264. Olsen M.H., Wachtell K., Beevers G., et al. Effects of losartan compared with atenolol on lipids in patients with hypertension and left ventricular hypertrophy: the Losartan Intervention For Endpoint reduction in hypertension study. J Hypertens 2009, 27(3):567-574.
265. Nishida Y., Takahashi Y., Nakayama T., et al. Effect of candesartan monotherapy on lipid metabolism in patients with hypertension: a retrospective longitudinal survey using data from electronic medical records. Cardiovasc Diabetol 2010, 9:38.