Peroxisome proliferator-activated receptor-alpha (PPARα): At the crossroads of obesity, diabetes and cardiovascular disease

Atherosclerosis

Volumn 205, Issue 1, 2009, Pages 1-8

  Fruchart, Jean Charles ^a  

^a INSERM   (France)

Author keywords

Cardiovascular; Inflammation; Lipoprotein metabolism; Microvascular; Peroxisome proliferator activated receptor ; Vascular function

Indexed keywords

BEZAFIBRATE; CLOFIBRATE; FENOFIBRATE; GEMFIBROZIL; GFT 505; HIGH DENSITY LIPOPROTEIN; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; INTERLEUKIN 6; LOW DENSITY LIPOPROTEIN; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA AGONIST; PLACEBO; SIMVASTATIN; TRIACYLGLYCEROL; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG;

ARTERY INTIMA PROLIFERATION; ATHEROGENESIS; ATHEROSCLEROSIS; ATHEROSCLEROTIC PLAQUE; CARDIOVASCULAR DISEASE; CAROTID ARTERY OBSTRUCTION; CHOLESTEROL TRANSPORT; CLINICAL TRIAL; CORONARY ARTERY ATHEROSCLEROSIS; DIABETIC RETINOPATHY; DRUG BLOOD LEVEL; DRUG MECHANISM; DRUG SAFETY; DYSLIPIDEMIA; FATTY ACID OXIDATION; HEART INFARCTION; HUMAN; HYPERLIPIDEMIA; INFLAMMATION; INSULIN RESISTANCE; LIPID METABOLISM; LIPOPROTEIN METABOLISM; METABOLIC SYNDROME X; MYOPATHY; NON INSULIN DEPENDENT DIABETES MELLITUS; NONALCOHOLIC FATTY LIVER; NONHUMAN; OBESITY; PRIORITY JOURNAL; REVIEW; RHABDOMYOLYSIS; RISK REDUCTION; VASCULAR SMOOTH MUSCLE;

ANIMALS; BIOLOGICAL TRANSPORT; CARDIOVASCULAR DISEASES; CHOLESTEROL; DIABETES MELLITUS; FATTY ACIDS; HUMANS; INFLAMMATION; LIPID METABOLISM; LIPIDS; LIPOPROTEINS; MICE; MICROCIRCULATION; OBESITY; PPAR ALPHA;

EID: 67449108376     PISSN: 00219150     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.atherosclerosis.2009.03.008     Document Type: Review

References (67)

1. Petersen S., Peto V., Rayner M., et al. European cardiovascular disease statistics (2005), British Heart Foundation, London
2. Diabetes prevalence. Available from International Diabetes Federation, www.idf.org. Accessed September 29, 2008.
3. U.S. Obesity trends 1985-2007. Available from Centers for Disease Control and Prevention, www.cdc.gov/nccdphp/dnpa/obesity/trend/maps/index.htm. Accessed September 29, 2008.
4. Chinetti-Gbaguidi G., Fruchart J.C., and Staels B. Role of the PPAR family of nuclear receptors in the regulation of metabolic and cardiovascular homeostasis: new approaches to therapy. Curr Opin Pharmacol 5 (2005) 177-183
5. Martin G., Schoonjans K., Lefebvre A.M., Staels B., and Auwerx J. Coordinate regulation of the expression of the fatty acid transport protein and acyl-CoA synthetase genes by PPARalpha and PPARgamma activators. J Biol Chem 272 (1997) 28210-28217
6. Schoonjans K., Peinado-Onsurbe J., Lefebvre A.M., et al. PPARalpha and PPARgamma activators direct a distinct tissue-specific transcriptional response via a PPRE in the lipoprotein lipase gene. EMBO J 15 (1996) 5336-5348
7. Prieur X., Coste H., and Rodriguez J.C. The human apolipoprotein AV gene is regulated by PPARα and contains a novel FXR response element. J Biol Chem 278 (2003) 25468-25480
8. Staels B., Vu-Dac N., Kosykh V., et al. Fibrates down-regulate apolipoprotein C-III expression independent of induction of peroxisomal acyl co-enzyme A oxidase. J Clin Invest 95 (1995) 705-712
9. Raspé E., Duez H., Mansén A., et al. Identification of Rev-erbalpha as a physiological repressor of apoC-III gene transcription. J Lipid Res 43 (2002) 2172-2179
10. Tomiyasu K., Walsh B.W., Ikewaki K., et al. Differential metabolism of human VLDL according to content of ApoE and ApoC-III. Arterioscler Thromb Vasc Biol 21 (2001) 1494-1500
11. Hiukka A., Fruchart-Najib J., Fruchart J.C., et al. Alterations of lipids and apolipoprotein CIII in very low density lipoprotein species in type 2 diabetes. Diabetologia 48 (2005) 1207-1215
12. Staels B., Dallongeville J., Auwerx J., et al. Mechanism of action of fibrates on lipid and lipoprotein metabolism. Circulation 98 (1998) 2088-2093
13. Chinetti G., Gbaguidi G.F., Griglio S., et al. CLA-SR-BI is expressed in atherosclerotic lesion macrophages and regulated by activators of peroxisome proliferator-activated receptors. Circulation 101 (2000) 2411-2417
14. Chinetti G., Lestavel S., Bocher V., et al. PPAR-alpha and PPAR-gamma activators induce cholesterol removal from human macrophage foam cells through stimulation of the ABCA1 pathway. Nat Med 7 (2001) 53-58
15. Chinetti G., Lestavel S., Fruchart J.C., Clavey V., and Staels B. Peroxisome proliferator-activated receptor alpha reduces cholesterol esterification in macrophages. Circ Res 92 (2003) 212-217
16. Chinetti-Gbaguidi G., Rigamonti E., Helin L., et al. Peroxisome proliferator-activated receptor α controls cellular cholesterol trafficking in macrophages. J Lipid Res 46 (2005) 2717-2725
17. Staels B., Koenig W., Habib A., et al. Activation of human aortic smooth-muscle cells is inhibited by PPARalpha but not PPARgamma activators. Nature 393 (1998) 790-793
18. Marx N., Sukhova G., Collins T., Libby P., and Plutzky J. PPARα activators inhibit cytokine-induced vascular cell adhesion molecule 1 expression in human endothelial cells. Circulation 99 (1999) 3125-3131
19. Neve B.P., Corseaux D., Chinetti G., et al. PPARα agonists inhibit tissue factor expression in human THP-1 cells, monocytes and macrophages. Circulation 103 (2001) 207-212
20. Delerive P., De Bosscher K., Besnard S., et al. PPARα negatively regulates the vascular inflammatory gene response by negative cross-talk with transcription factors NF-κB and AP-1. J Biol Chem 274 (1999) 32048-32054
21. Lee H., Shi W., Tontonoz P., et al. Role for peroxisome proliferator-activated receptor alpha in oxidized phospholipid-induced synthesis of monocyte chemotactic protein-1 and interleukin-8 by endothelial cells. Circ Res 87 (2000) 516-521
22. Pasceri V., Cheng J.S., Willerson J.T., and Yeh ET. Modulation of C-reactive protein-mediated monocyte chemoattractant protein-1 induction in human endothelial cells by anti-atherosclerosis drugs. Circulation 103 (2001) 2531-2534 [Erratum in: Circulation 2001 ;104(October(16)):1992. Chang J [corrected to Cheng JS]]
23. 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 85 (1999) 394-402
24. Valenti L., Fracanzani A.L., Dongiovanni P., et al. Tumor necrosis factor alpha promoter polymorphisms and insulin resistance in nonalcoholic fatty liver disease. Gastroenterology 122 (2002) 274-280
25. Marx N., Kehrle B., Kohlhammer K., et al. PPAR activators as anti-inflammatory mediators in human T lymphocytes, implications for atherosclerosis and transplantation-associated arteriosclerosis. Circ Res 90 (2002) 703-710
26. Delerive P., Gervois P., Fruchart J.C., and Staels B. Induction of IκBα expression as a mechanism contributing to the anti-inflammatory activities of PPARα activators. J Biol Chem 275 (2000) 36703-36707
27. Madej A., Okopien B., Kowalski J., et al. Effects of fenofibrate on plasma cytokine concentrations in patients with atherosclerosis and hyperlipoproteinemia IIb. Int J Clin Pharmacol Ther 36 (1998) 345-349
28. Ip E., Farrell C., Robertson G., et al. Central role of PPARα-dependent hepatic lipid turnover in dietary steatohepatitis in mice. Hepatology 38 (2003) 123-132
29. Fernández-Miranda C., Pérez-Carreras M., Colina F., et al. A pilot trial of fenofibrate for the treatment of non-alcoholic fatty liver disease. Dig Liver Dis 40 (2008) 200-205
30. Shu H., Wong B., Zhou G., et al. Activation of PPARalpha or gamma reduces secretion of matrix metalloproteinase 9 but not interleukin 8 from human monocyte THP-1 cells. Biochem Biophys Res Commun 267 (2000) 345-349
31. Chinetti G., Griglio S., Antonucci M., et al. Activation of peroxisome proliferator-activated receptors α and γ induces apoptosis of human monocyte-derived macrophages. J Biol Chem 273 (1998) 25573-25580
32. Neve B.P., Corseaux D., Chinetti G., et al. PPARα agonists inhibit tissue factor expression in human monocytes and macrophages. Circulation 103 (2001) 207-212
33. Nilsson B., Banfi C., Diczfalusy U., et al. Unsaturated fatty acids increase plasminogen activator inhibitor-1 expression in endothelial cells. Arterioscler Thromb Vasc Biol 18 (1998) 1679-1685
34. Durrington P.N., Mackness M.I., Bhatnagar D., et al. Effects of two different fibric acid derivatives on lipoproteins, cholesteryl ester transfer, fibrinogen, plasminogen activator inhibitor and paraoxonase activity in type IIb hyperlipoproteinaemia. Atherosclerosis 138 (1998) 217-225
35. INK4a. J Clin Invest 115 (2005) 3228-3238
36. Kersten S., Seydoux J., Peters J.M., et al. Peroxisome proliferator-activated receptor alpha mediates the adaptive response to fasting. J Clin Invest 103 (1999) 1489-1498
37. Guerre-Millo M., Gervois P., Raspé E., et al. Peroxisome proliferator-activated receptor alpha activators improve insulin sensitivity and reduce adiposity. J Biol Chem 275 (2000) 16638-16642
38. Stienstra R., Mandard S., Patsouris D., et al. Peroxisome proliferator-activated receptor alpha protects against obesity-induced hepatic inflammation. Endocrinology 148 (2007) 2753-2763
39. Yessoufou A., Atègbo J.M., Attakpa E., et al. Peroxisome proliferator-activated receptor-alpha modulates insulin gene transcription factors and inflammation in adipose tissues in mice. Mol Cell Biochem November (2008) [Epub ahead of print]
40. Tsuchida A., Yamauchi T., Takekawa S., et al. Peroxisome proliferator-activated receptor (PPAR)alpha activation increases adiponectin receptors and reduces obesity-related inflammation in adipose tissue: comparison of activation of PPARalpha, PPARgamma, and their combination. Diabetes 54 (2005) 3358-3370
41. Cholesterol Treatment Trialists' (CTT) Collaborators, Kearney P.M., Blackwell P.M., et al. Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: a meta-analysis. Lancet 371 (2008) 117-125
42. Barter P.J., Gotto A.M., LaRosa J.C., et al. Treating to New Targets Investigators. HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events. N Engl J Med 357 (2007) 1301-1310
43. Miller M., Cannon C.P., Murphy S.A., et al. PROVE-IT TIMI 22 Investigators. Impact of triglyceride levels beyond low-density lipoprotein cholesterol after acute coronary syndrome in the PROVE-IT TIMI 22 trial. J Am Coll Cardiol 51 (2008) 724-730
44. 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. N Engl J Med 341 (1999) 410-418
45. 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 162 (2002) 2597-2604
46. The BIP Study group. Secondary prevention by raising HDL cholesterol and reducing triglycerides in patients with coronary artery disease. The bezafibrate infarction prevention (BIP) study. Circulation 102 (2000) 21-27
47. Tenenbaum A., Motro M., Fisman E.Z., et al. Bezafibrate for the secondary prevention of myocardial infarction in patients with metabolic syndrome. Arch Intern Med 165 (2005) 1154-1160
48. Frick M.H., Elo O., Haapa K., et al. Helsinki Heart Study: primary prevention trial with gemfibrozil in middle-aged men with dyslipidemia. N Engl J Med 317 (1987) 1237-1245
49. Tenkanen L., Mantarri M., and Manninen V. Some coronary risk factors related to the insulin resistance syndrome and treatment with gemfibrozil: experience from the Helsinki Heart Study. Circulation 92 (1995) 1779-1785
50. Keech A., Simes R.J., Barter P., et al. The FIELD study investigators. Effect of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Lancet 366 (2005) 1849-1861
51. Scott R., O'Brien R., Fulcher G., et al. The effects of fenofibrate treatment on cardiovascular disease risk in 9795 people with type 2 diabetes and various components of the metabolic syndrome: the FIELD study. Diabetes Care (2008) 10.2337/dc08-1543 published on-line November 4, 2008
52. DAIS Investigators. DAIS: effect of fenofibrate on progression of coronary-artery disease in type 2 diabetes: The Diabetes Atherosclerosis Intervention Study, a randomised study. Lancet 357 (2001) 905-910
53. Bloomgarden Z.T. Second world congress on the insulin resistance syndrome. Diabetes Care 28 (2005) 2073-2080
54. Coban E., and Sari R. The effect of fenofibrate on the levels of high sensitivity C-reactive protein in dyslipidemic obese patients. Endocr Res 30 (2004) 343-349
55. Grundy S.M., Vega G.L., Yuan Z., et al. Effectiveness and tolerability of simvastatin plus fenofibrate for combined hyperlipidemia (the SAFARI trial). Am J Cardiol 95 (2005) 462-468
56. Jones P.H., and Davidson M.H. Reporting rate of rhabdomyolysis with fenofibrate + statin versus gemfibrozil + any statin. Am J Cardiol 95 (2005) 120-122
57. Prueksaritanont T., Tang C., Qiu Y., et al. Effects of fibrates on metabolism of statins in human hepatocytes. Drug Metab Dispos 30 (2002) 1280-1287
58. Gaede P., Vedel P., Larsen N., et al. Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med 348 (2003) 383-393
59. Keech A.C., Mitchell P., Summanen P.A., et al. FIELD Study Investigators, effect of fenofibrate on the need for laser treatment for diabetic retinopathy (FIELD study): a randomised controlled trial. Lancet 370 (2007) 1687-1697
60. Sato M. Peroxisome proliferator activated receptor ligands and angiogenesis. Nippon Rinsho 63 (2005) 603-608
61. Panigrahy D., Kaipainen A., Huang S., et al. PPARalpha agonist fenofibrate suppresses tumor growth through direct and indirect angiogenesis inhibition. Proc Natl Acad Sci USA 105 (2008) 985-990
62. Wilkinson-Berka J.L., Wraight C., and Werther G. The role of growth hormone, insulin-like growth factor and somatostatin in diabetic retinopathy. Curr Med Chem 13 (2006) 3307-3317
63. Kim J., Ahn J.H., Yu Y.S., et al. Fenofibrate regulates retinal endothelial cell survival through the AMPK signal transduction pathway. Exp Eye Res 84 (2007) 886-893
64. Kamijo Y., Hora K., Tanaka N., et al. Identification of functions of peroxisome proliferator-activated receptor alpha in proximal tubules. J Am Soc Nephrol 13 (2002) 1691-1702
65. Duez H., Lefebvre B., Poulain P., et al. Regulation of human apoA-I by gemfibrozil and fenofibrate through selective peroxisome proliferator-activated receptor α modulation. Arterioscler Thromb Vasc Biol 25 (2005) 585-591
66. Fruchart J.C. Novel peroxisome proliferator activated-receptor-α agonists. Am J Cardiol 100 suppl (2007) 41N-46N
67. Colman P, Rajamani K, Li L-P et al. Benefits of long-term fenofibrate therapy on amputations in type 2 diabetes mellitus in the FIELD trial. Presented at the European Association for the study of Diabetes (EASD), Rome, September 2008.