Modulation of hepatic inflammatory risk markers of cardiovascular diseases by PPAR-α activators: Clinical and experimental evidence

Arteriosclerosis, Thrombosis, and Vascular Biology

Volumn 26, Issue 5, 2006, Pages 977-986

  Zambon, Alberto ^d   Gervois, Philippe ^a,b,c   Pauletto, Paolo ^d   Fruchart, Jean Charles ^a,b,c   Staels, Bart ^a,b,c  

^a INSTITUT PASTEUR DE LILLE   (France)

^b INSERM   (France)

^c UNIV LILLE   (France)

^d UNIVERSITY OF PADOVA   (Italy)

Author keywords

Atherosclerosis; C reactive protein; Fibrates; Inflammation; Peroxisome proliferator activated receptors

Indexed keywords

ANTILIPEMIC AGENT; ATORVASTATIN; BEZAFIBRATE; C REACTIVE PROTEIN; CELL ADHESION MOLECULE; CIPROFIBRATE; CYTOKINE; EZETIMIBE; FATTY ACID; FENOFIBRATE; FIBRIC ACID DERIVATIVE; FIBRINOGEN; GELATINASE B; GEMFIBROZIL; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; INTERLEUKIN 1; INTERLEUKIN 6; LIGAND; LIPOPROTEIN; LOW DENSITY LIPOPROTEIN; LOW DENSITY LIPOPROTEIN CHOLESTEROL; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA AGONIST; PROCOAGULANT; SIMVASTATIN; TRANSCRIPTION FACTOR; TRIACYLGLYCEROL; TUMOR NECROSIS FACTOR ALPHA; UNINDEXED DRUG; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; PROTEIN C JUN;

ACUTE PHASE RESPONSE; ATHEROGENESIS; ATHEROSCLEROSIS; BLOOD CLOTTING; BLOOD VESSEL REACTIVITY; CANCER RISK; CARDIOVASCULAR DISEASE; CLINICAL PRACTICE; CLINICAL TRIAL; CORONARY ARTERY DISEASE; DEEP VEIN THROMBOSIS; DRUG MECHANISM; GENE EXPRESSION REGULATION; HEART PROTECTION; HUMAN; HYPERTRIGLYCERIDEMIA; IMMUNOMODULATION; INFLAMMATION; LIPID METABOLISM; LIVER; LUNG EMBOLISM; METABOLIC SYNDROME X; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PANCREATITIS; PRIORITY JOURNAL; SHORT SURVEY; ANIMAL; BLOOD; DRUG POTENTIATION; LIVER CELL; METABOLISM; MONOCYTE; PHOSPHORYLATION; PHYSIOLOGY; REVIEW; SIGNAL TRANSDUCTION; VASCULAR ENDOTHELIUM;

ANIMALS; ATHEROSCLEROSIS; C-REACTIVE PROTEIN; CHOLESTEROL, LDL; CORONARY DISEASE; ENDOTHELIUM, VASCULAR; FIBRINOGEN; HEPATOCYTES; HUMANS; INFLAMMATION; INTERLEUKIN-6; MONOCYTES; NF-KAPPA B; PHOSPHORYLATION; PPAR ALPHA; PROTO-ONCOGENE PROTEINS C-JUN; SIGNAL TRANSDUCTION;

EID: 33646440029     PISSN: 10795642     EISSN: None     Source Type: Journal    
DOI: 10.1161/01.ATV.0000204327.96431.9a     Document Type: Short Survey

References (113)

1. Issemann I, Green S. Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature. 1990;347:645-650.
2. Kliewer SA, Lenhard JM, Willson TM, Patel I, Morris DC, Lehmann JM. A prostaglandin J2 metabolite binds peroxisome proliferator-activated receptor gamma and promotes adipocyte differentiation. Cell. 1995;83:813-819.
3. Forman BM, Chen J, Evans RM. Hypolipidemic drugs, polyunsaturated fatty acids, and eicosanoids are ligands for peroxisome proliferator-activated receptors alpha and delta. Proc Natl Acad Sci U S A. 1997;94:4312-4317.
4. Devchand PR, Keller H, Peters JM, Vazquez M, Gonzalez FJ, Wahli W. The PPAR-alpha-leukotriene B4 pathway to inflammation control. Nature. 1996;384:39-43.
5. Nagy L, Tontonoz P, Alvarez JG, Chen H, Evans RM. Oxidized LDL regulates macrophage gene expression through ligand activation of PPAR-γ. Cell. 1998;93:229-240.
6. Delerive P, Furman C, Teissier E, Fruchart J, Duriez P, Staels B. Oxidized phospholipids activate PPAR-alpha in a phospholipase A2-dependent manner. FEBS. 2000;471:34-38.
7. Lehmann JM, Moore LB, Smith-Oliver TA, Wilkison WO, Willson TM, Kliewer SA. An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor gamma (PPAR gamma). J Biol Chem. 1995;270:12953-12956.
8. Ijpenberg A, Jeannin E, Wahli W, Desvergne B. Polarity and specific sequence requirements of peroxisome proliferator-activated receptor (PPAR-)/retinoid X receptor heterodimer binding to DNA. A functional analysis of the malic enzyme gene PPAR response element. J Biol Chem. 1997;272:20108-20117.
9. Gervois P, Chopin-Delannoy S, Fadel A, Dubois G, Kosykh V, Fruchart JC, Najib J, Laudet V, Staels B. Fibrates increase human REV-ERBalpha expression in liver via a novel peroxisome proliferator-activated receptor response element. Mol Endocrinol. 1999;13:400-409.
10. Kersten S, Seydoux J, Peters JM, Gonzalez FJ, Desvergne B, Wahli W. Peroxisome proliferator-activated receptor alpha mediates the adaptive response to fasting. J Clin Invest. 1999;103:1489-1498.
11. Leone TC, Weinheimer CJ, Kelly D. A crtical role for the peroxisome proliferator-activated receptor alpha (PPAR-alpha) in the cellular fasting response: the PPAR-alpha-null mouse as a model of fatty acid oxidation disorders. Proc Natl Acad Sci U S A. 1999;96:7473-7478.
12. Guerre-Millo M, Gervois P, Raspe E, Madsen L, Poulain P, Derudas B, Herbert JM, Winegar DA, Willson TM, Fruchart JC, Berge RK, Staels B. Peroxisome proliferator-activated receptor alpha activators improve insulin sensitivity and reduce adiposity. J Biol Chem. 2000;275:16638-16642.
13. Gervois P, Torra IP, Fruchart JC, Staels B. Regulation of lipid and lipoprotein metabolism by PPAR activators. Clin Chem Lab Med. 2000;38:3-11.
14. Marx N, Sukhova G, Collins T, Libby P, Plutzky J. PPAR-α activators inhibit cytokine-induced vascular cell adhesion molecule-1 expression in human endothelial cells. Circulation. 1999;99:3125-3131.
15. Delerive P, De Bosscher K, Besnard S, Vanden Berghe W, Peters JM, Gonzalez FJ, Fruchart JC, Tedgui A, Haegeman G, Staels B. Peroxisome proliferator-activated receptor alpha negatively regulates the vascular inflammatory gene response by negative cross-talk with transcription factors NF-kappaB and AP-1. J Biol Chem. 1999;274:32048-32054.
16. Staels B, Koenig W, Habib A, Merval R, Lebret M, Torra IP, Delerive P, Fadel A, Chinetti G, Fruchart JC, Najib J, Maclouf J, Tedgui A. Activation of human aortic smooth-muscle cells is inhibited by PPAR-alpha but not by PPAR-gamma activators. Nature. 1998;393:790-793.
17. Gervois P, Kleemann R, Pilon A, Koenig W, Staels B, Kooistra T. Global suppression of IL-6-induced acute phase response gene expression after in vivo chronic treatment with the peroxisome proliferator-activated receptor α activator fenofibrate. J Biol Chem. 2004;279:16154-16160.
18. Ross R. Atherosclerosis: an inflammatory disease. N Engl J Med. 1999;340:115-126.
19. Delerive P, Martin-Nizard F, Chinetti G, Trottein F, Fruchart JC, Duriez P, Staels B. PPAR activators inhibit thrombin-induced endothelin-1 production in human vascular endothelial cells by inhibiting the AP-1 signaling pathway. Circ Res. 1999;85:394-402.
20. Jackson SM, Parhami F, Xi XP, Berliner JA, Hsueh WA, Law RE, Demer LL. Peroxisome proliferator-activated receptor activators target human endothelial cells to inhibit leukocyte-endothelial cell interaction. Arterioscler Thromb Vasc Biol. 1999;19:2094-2104.
21. Marx N, Mackman N, Schönbeck U, Yilmaz N, Hombach VV, Libby P, Plutzky J. PPAR-alpha activators inhibit tissue factor expression and activity in human monocytes. Circulation. 2001;103:213-219.
22. Neve BP, Corseaux D, Chinetti G, Zawadzki C, Fruchart J-C, Duriez P, Staels B, Jude B. PPAR-alpha agonists inhibit tissue factor expression in human monocytes and macrophages. Circulation. 2001;103:207-212.
23. Streetz KL, Wustefeld T, Klein C, Manns MP, Trautwein C. Mediators of inflammation and acute phase response in the liver. Cell Mol Biol. 2001;47:661-673.
24. Yudkin JS, Kumari M, Humphries SE, Mohamed-Ali V. Inflammation, obesity, stress and coronary heart disease: is interleukin-6 the link? Atherosclerosis. 2000;148:209-214.
25. Dhainaut JF, Marin N, Mignon A, Vinsonneau C. Hepatic response to sepsis: interaction between coagulation and inflammatory processes. Crit Care Med. 2001;29:S42-S47.
26. Hoffmeister A, Rothenbacher D, Bazner U, Frohlich M, Brenner H, Hombach V, Koenig W. Role of novel markers of inflammation in patients with stable coronary heart disease. Am J Cardiol. 2001;87:262-266.
27. Ridker PM, Rifai N, Pfeffer MA, Sacks FM, Moye LA, Goldman S, Flaker GC, Braunwald E. Inflammation, pravastatin, and the risk of coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events (CARE) Investigators. Circulation. 1998;98:839-844.
28. Ridker PM, Stampfer MJ, Rifai N. Novel risk factors for systemic atherosclerosis: a comparison of C-reactive protein, fibrinogen, homocysteine, lipoprotein(a), and standard cholesterol screening as predictors of peripheral arterial disease. JAMA. 2001;285:2481-2485.
29. Sirtori CR, Colli S. Influences of lipid-modifying agents on hemostasis. Cardiovasc Drugs Ther. 1993;7:817-823.
30. Jonkers IJ, Mohrschladt MF, Westendorp RG, van der Laarse A, Smelt AH. Severe hypertriglyceridemia with insulin resistance is associated with systemic inflammation: reversal with bezafibrate therapy in a randomized controlled trial. Am J Med. 2002;275-280.
31. Gervois P, Vu-Dac N, Kleemann R, Kockx M, Dubois G, Laine B, Kosykh V, Fruchart JC, Kooistra T, Staels B. Negative regulation of human fibrinogen gene expression by peroxisome proliferator-activated receptor alpha agonists via inhibition of CCAAT box/enhancer-binding protein beta. J Biol Chem. 2001;276:33471-33477.
32. Kleemann R, Gervois P, Verschuren L, Staels B, Princen HM, Kooistra T. Fibrates down-regulate IL-1-stimulated C-reactive protein gene expression in hepatocytes by reducing p50-NF-kB-C/EBP-b complex formation. Blood. 2003;101:545-551.
33. Baumann H, Morella KK, Campos SP, Cao Z, Jahreis GP. Role of CAAT-enhancer binding protein isoforms in the cytokine regulation of acute-phase plasma protein genes. J Biol Chem. 1992;267:19744-19751.
34. Zauberman A, Lapter S, Zipori D. Smad proteins suppress CCAAT/enhancer-binding protein (C/EBP) beta- and STAT3-mediated transcriptional activation of the haptoglobin promoter. J Biol Chem. 2001;276:24719-24725.
35. Kordula T, Travis J. The role of Stat and C/EBP transcription factors in the synergistic activation of rat serine protease inhibitor-3 gene by interleukin-6 and dexamethasone. Biochem J. 1996;313:1019-1027.
36. Schuringa JJ, Timmer H, Luttickhuizen D, Vellenga E, Kruijer W. c-Jun and c-Fos cooperate with STAT3 in IL-6-induced transactivation of the IL-6 response element (IRE). Cytokine. 2001;14:78-87.
37. Yoo JY, Wang W, Desiderio S, Nathans D. Synergistic activity of STAT3 and c-Jun at a specific array of DNA elements in the alpha 2-macroglobulin promoter. J Biol Chem. 2001;276:26421-26429.
38. Delerive P, Gervois P, Fruchart JC, Staels B. Induction of IkappaBalpha expression as a mechanism contributing to the anti-inflammatory activities of peroxisome proliferator-activated receptor-alpha activators. J Biol Chem. 2000;275:36703-36707.
39. Morishima A, Okhubo N, Maeda N, Miki T, Mitsuda N. NF-kappaB regulates plasma apolipoprotein A-I and high density lipoprotein cholesterol through inhibition of peroxisome proliferator activated receptor alpha. J Biol Chem. 2003;278:38188-38193.
40. Lusis AJ.Atherosclerosis Nature. 2000;407:233-241.
41. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detections, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult treatment Panel III). JAMA. 2001;285:2486-2497.
42. Ridker PM, Buring JE, Cook NR, Rifai N. C-Reactive protein, the metabolic syndrome, and risk of incident cardiovascular events: an 8-year follow-up of 14 719 initially healthy american women. Circulation. 2003;107:391-397.
43. 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.
44. Bonora E, Kiechl S, Willeit J, Oberhollenzer F, Egger G, Bonadonna RC, Muggeo M. Metabolic Syndrome: epidemiology and more extensive phenotypic description. Cross-sectional data from the Bruneck Study. International Journal of Obesity. Int J Obes. 2003;27:1283-1289.
45. Onat A, Ceyhan K, Basar O, Erer B, Toprak S, Sansoy V. Metabolic syndrome: major impact on coronary risk in a population with low cholesterol levels - a prospective and cross-sectional evaluation. Atherosclerosis. 2002;165:285-292.
46. Isomaa B, Almgren P, Tuomi T, Forsen B, Lahti K, Nissen M, Taskinen MR, Groop L. Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care. 2001;24:683-689.
47. Frick MH, Elo O, Haapa K, Heionen OP, Heinsalmi P, Helo P, Huttunen JK, Kaitaniemi P, Koskinen P, Manninen V. Helsinki Heart Study: primary prevention trial with gemfibrozil in middle-aged men with dysilidemia. Safety of treatment, changes in risk factors, and incidence of coronary heart disease. N Engl J Med. 1987;317:1237-1245.
48. Rubins HB, Robins SJ, Collins D, Fye CL, Anderson JW, Elam MB, Faas FH, Linares E, Schaefer EJ, Schectman G, Wilt TJ, Wittes J. 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;341:410-418.
49. Ericsson CG, Hamsten A, Nilsson J, Grip L, Svane B, de Faire U. Angiographic assessment of effects of bezafibrate on progress of coronary artery disease in young male postinfarction patients. Lancet. 1996;347:849-853.
50. Frick MH, Syvanne M, Nieminen MS, Kauma H, Majahalme S, Virtanen V, Kesaniemi YA, Pasternack A, Taskinen MR. Prevention of the angiographic progression of coronary and vein-graft atherosclerosis by gemfibrozil after coronary bypass surgery in men with low levels of HDL cholesterol. Lopid Coronary Angiography Trial (LOCAT) Study Group. Circulation. 1997;96:2137-2143.
51. DAIS: Effect of fenofibrate on progression of coronary-artery disease in type 2 diabetes: the Diabetes Atherosclerosis Intervention Study, a randomised study. Lancet. 2001;357:905-910.
52. The FIELD investigators. 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;366:1849-1861.
53. Hennuyer N, Tailleux A, Torpier G, Mezdour H, Fruchart J-C, Staels B, Fievet C. PPAR-a, but not PPAR-g, activators decrease macrophage-laden atherosclerotic lesions in a nondiabetic mouse model of mixed dyslipidemia. Arterioscler Thromb Vasc Biol. 2005;25:1897-1902.
54. Duez H, Chao YS, Hernandez M, Torpier G, Poulain P, Mundt S, Mallat Z, Teissier E, Burton CA, Tedgui A, Fruchart J-C, Fievet C, Wright SD, Staels B. Reduction of atherosclerosis by the peroxisome proliferator-activated receptorα agonist fenofibrate in mice. J Biol Chem. 2002;277:48051-48057.
55. Li AC, Binder CJ, Gutierrez A, Brown KK, Plotkin CR, Pattison JW, Valledor AP, Davis RA, Willson TM, Witztum JL, Palinski W, Glass CK. Differential inhibition of macrophage foam-cell formation and atherosclerosis in mice by PPAR-a, b/d, and g. J Clin Invest. 2004;114:1538-1540.
56. Tordjman K, Bernal-Mizrachi C, Zemany L, Weng S, Feng C, Zhang F, Leone TC, Coleman T, Kelly DP, Semenkovich CF. PPAR-α deficiency reduces insulin resistance and atherosclerosis in apoE-null mice. J Clin Invest. 2001;107:1025-1034.
57. Lee SS, Pineau T, Drago J, Lee EJ, Owens JW, Kroetz DL, Fernandez-Salguero PM, Westphal H, Gonzalez FJ. Targeted disruption of the alpha isoform of the peroxisome proliferator- activated receptor gene in mice results in abolishment of the pleiotropic effects of peroxisome proliferators. Mol Cell Biol. 1995;15:3012-3022.
58. Huttunen JK, Heinonen OP, Manninen V, Koskinen P, Hakulinen T, Teppo L, Manttari M, Frick MH. The Helsinki Heart Study: an 8.5-year safety and mortality follow-up. J Intern Med. 1994;235:31-39.
59. Childs M, Girardot G. Evaluation of acquired data on long-term risk of hypolipidemic treatment. Arch Mal Coeur Vaiss. 1992;85:129-133.
60. Cheung C, Akiyama TE, Ward JM, Nicol CJ, Feigenbaum L, Vinson C, Gonzalez FJ. Diminished hepatocellular proliferation in mice humanized for the nuclear receptor peroxisome proliferator-activated receptorα. Cancer Res. 2004;64:3849-3854.
61. Calabresi L, Gomaraschi M, Villa B, Omoboni L, Dmitrieff C, Franceschini G. Elevated soluble cellular adhesion molecules in subjects with low HDL-cholesterol. Arterioscler Thromb Vasc Biol. 2002;22:656-661.
62. Madej A, Okopien B, Kowalski J, Zielinski M, Wysocki J, Szygula B, Kalina Z, Herman ZS. Effects of fenofibrate on plasma cytokine concentrations in patients with atherosclerosis and hyperlipoproteinemia IIb. Int J Clin Pharmacol Ther. 1998;36:345-349.
63. Pasceri V, Cheng JS, Willerson JT, Yeh ET, Chang J. Modulation of C-reactive protein-mediated monocyte chemoattractant protein-1 induction in human endothelial cells by anti-atherosclerosis drugs. Circulation. 2001;103:2531-2534.
64. Kowalski J, Okopien B, Madej A, Zielinski M, Belowski D, Kalina Z, Herman ZS. Effects of fenofibrate and simvastatin on plasma sICAM and MCP-1 concentrations in patients with hyperlipoproteinemia. Int J Clin Pharmacol Ther. 2003;41:241-247.
65. Verma S, Buchanan MR, Anderson TJ. Endothelial function testing as biomarker of vascular disease. Circulation. 2003;108:2054-2059.
66. Anderson TJ. Assessment and treatment of endothelial dysfunction in humans. J Am Coll Cardiol. 1999;34:631-638.
67. Malik J, Melenovsky V, Wichterle D, Haas T, Simek T, Ceska R, Hradec J. Both fenofibrate and atorvastatin improve vascular reactivity in combined hyperlipidemia. Cardiovasc Res. 2001;52:290-298.
68. Capell WH, DeSouza CA, Poirier P, Bell ML, Stauffer BL, Weil KM, Hernandez TL, Eckel RM. Short-term triglyceride lowering with fenofibrate improves vasodilator function in subjects with hypertriglyceridemia. Arterioscler Thromb Vasc Biol. 2003;23:307-313.
69. Evans M, Anderson RA, Graham J, Ellis G, Morris K, Davies S, Jackson SK, Lewis MJ, Frenneaux MP, Rees A. Ciprofibrate therapy improves endothelial function and reduces postprandial lipemia and oxidative stress in type 2 diabetes mellitus. Circulation. 2000;101:1773-1779.
70. Avogaro A, Miola RA, Favaro A, Gottardo L, Pacini G, Manzato E, Zambon S, Sacerdoti D, de Kreutzenberg S, Piliego T, Del Prato S. Gemfibrozil improves insulin sensitivity and flow-mediated vasodilatation in type 2 patients. Eur J Clin Invest. 2001;31:603-609.
71. Playford DA, Watts GF, Best JD, Burke V. Effect of fenofibrate on brachial artery flow-mediated dilatation in type 2 diabetes mellitus. Am J Cardiol. 2002;90:1254-1257.
72. Playford DA, Watts GF, Croft KD, Burke V. Combined effect of coenzyme Q10 and fenofibrate on forearm microcirculatory function in type 2 diabetes. Atherosclerosis. 2003;168:169-179.
73. Davies MJ, Thomas AC. Plaque fissuring: the cause of acute myocardial infarction, sudden ischemic death, and crescendo angina. Br Heart J. 1985;53:363-373.
74. Libby P. Molecular bases of the acute coronary syndromes. Circulation. 1995;91:2844-2850.
75. Shu H, Wong B, Zhou G, Li Y, Berger J, Woods JW, Wright SD, Cai TQ. Activation or PPAR-alpha of gamma reduces secretion of matrix metalloproteinase 9 but not interleukin-8 from human monocytic THP-1 cells. Biochem Biophys Res Commun. 2000;267:345-349.
76. Eberhardt W, Akool el S, Rebhan J, Frank S, Beck KF, Franzen R, Hamada FM, Pfeilschifter J. Inhibition of cytokine-induced matrix metalloproteinase 9 expression by peroxisome proliferator-activated receptor alpha agonists is indirect and due to a NO-mediated reduction of mRNA stability. J Biol Chem. 2002;277:33518-33528.
77. Huber K, Chris G, Wojta J, Gulba D. Plasminogen activator inhibitor type-1 in cardiovascular disease: Status Report 2001. Thromb Res. 2001;103:S7.
78. Fujii S, Sobel BE. Direct effects of gemfibrozil on the fibrinolitic system. Circulation. 1992;85:1888-1893.
79. Nillson L, Takemura T, Eriksson P, Hamsten A. Effect of fibrates compounds on expression of plasminogen activator inhibitor-1 by cultured endothelial cells. Arterioscler Thromb Vasc Biol. 1999;19:1577-1581.
80. Lind L. Circulating markers of inflammation and atherosclerosis. Atherosclerosis. 2003;169:203-214.
81. Schonfeld G. The effects of fibrates on lipoprotein and hemostatic coronary risk factors. Atherosclerosis. 1994;111:161-174.
82. Turpin G, Bruckert E. Efficacy and safety of ciprofibrate in hyperlipoproteinemias. Atherosclerosis. 1996;124:S83-S87.
83. Maison P, Mennen L, Sapinho D, Balkau B, Sigalas J, Chesnier M-C, Eschwege E. DESIR Study Group. A pharmacological assessment of the effect of statins and fibrates on fibrinogen concentration. Arteriosclerosis. 2002;160:155-160.
84. Genest J, Nguyen NH, Theroux P, Davignon J, Cohn JS. Effect of micronized fenofibrate on plasma lipoprotein levels and hemostatic parameters of hypertriglyceridemic patients with low levels of high-density lipoprotein cholesterol in the fed and fasted state. J Cardiovasc Pharmacol. 2000;35:164-172.
85. Farnier M, Freeman MW, MacDonell G, Perevozskaya I, Davies MJ, Mitchel YB, Gumbiner B. Ezetimibe Study Group. Efficacy and safety of the coadministration of ezetimibe with fenofibrate in patients with mixed hyperlipidaemia. Eur Heart J. 2005;26:897-905.
86. Barbier O, Pineda Torra I, Duguay Y, Blanquart C, Fruchart J-C, Glineur C, Staels B. Pleiotropic actions of peroxisome proliferator-activated receptors in lipid metabolism and atherosclerosis. Arterioscler Thromb Vasc Biol. 2002;22:717-726.
87. Rizos E, Kostoula A, Elisaf M, Mikhailidis DP. Effect of ciprofibrate on C-reactive protein and fibrinogen levels. Angiology. 2002;53:273-277.
88. Després JP, Lemieux I, Pascot A, Alméras N, Dumont M, Nadeau A, PrudHomme D. Gemfibrozil reduces plasma C-reactive protein levels in abdominally obese men with the atherogenic dyslipidemia of the metabolic syndrome. Arterioscler Thromb Vasc Biol. 2003;23:702-703.
89. Wang TD, Chen WJ, Lin JW, Cheng CC, Chen MF, Lee YT. Efficacy of fenofibrate and simvastatin on endothelial function and inflammatory markers in patients with combined hyperlipidemia: relations with baseline lipid profiles. Atherosclerosis. 2003;170:315-323.
90. Kleemann R, Verschuren L, De Rooij BJ, Lindeman J, De Maat MM, Szalai AJ, Princen HM, Kooistra T. Evidence of anti-inflammatory activity of statins and PPAR-a activators in human C-reactive protein transgenic mice in vivo and in cultured human hepatocytes in vitro. Blood. 2004;103:4188-4194.
91. Willson TM, Wahli W. Peroxisome proliferator-activated receptor agonists. Curr Opin Chem Biol. 1997;1:235-241.
92. Simpson IA, Lorimer AR, Walker ID, Davidson JF. Effect of fibrate on platelet aggregation and fibrinolysis in patients with hypercholesterolemia. Thromb Haemost. 1989;54:442-444.
93. Genest JJ, McNamara JR, Ordovas JM, Jenner JL, Silberman SR, Anderson KM, Wilson PW, Salem DN, Schaefer EJ. Lipoprotein cholesterol, apolipoprotein A-I and B and lipoprotein (a) abnormality in men with premature coronary artery disease. J Am Coll Cardiol. 1992;19:792-802.
94. Austin MA, Breslow JL, Hennekens CH, Buring JE, Willett WC, Krauss RM. Low-density lipoprotein subclass patterns and risk of myocardial infarction. JAMA. 1988;260:1917-1921.
95. Superko HR. Beyond LDL cholesterol reduction. Circulation. 1996;94:2351-2354.
96. Williams PT, Superko HR, Haskell WL, Alderman EL, Blanche PJ, Blanche PJ, Holl LG, Krauss RM. Smallest LDL particles are most strongly related to coronary disease progression in men. Arterioscler Thromb Vasc Biol. 2002;23:314-321.
97. de Graaf J, Hak-Lemmers H, Hectors M, Demacker P, Hendriks J, Stalenhof AFH. Enhanced susceptibility to in vitro oxidation of the dense low density lipoprotein subfraction in healthy subjects. Arterioscler Thromb. 1991;11:298-306.
98. Lemieux I, Lapierre L, Dzavik V, Tremblay G, Bourgeois J, Després JP. A 16-week fenofibrate treatment increases LDL particle size in type IIA dyslipidemic patients. Atherosclerosis. 2002;162:363-371.
99. Vakkilainen J, Steiner G, Ansquer J-C, Aubin F, Rattier S, Foucher C, Hamsten A, Taskinen M-R. On behalf of the DAIS Group. Relationship between low-density lipoprotein particle size, plasma lipoproteins, and progression of coronary artery disease. Circulation. 2003;107:1733-1737.
100. Lemieux I, Salomon H, Després J-P. Contribution of apo CIII reduction to the greater effect of 12-week micronized fenofibrate than atorvastatin therapy on triglyceride levels and LDL size in dyslipidemic patients. Ann Med. 2003;35:442-448.
101. Melenovsky V, Malik J, Wichterle D, Simek J, Pisarikova A, Skrha J, Poledne R, Stavek P, Ceska R. Comparison of the effects of atorvastatin on non-lipid biochemical risk factors and LDL particle size in subjects with combined hyperlipidemia. Am Heart J. 2002;144:G1-G8.
102. Geiss HC, Dietlein M, Parhofer KG. Influence of fenofibrate on LDL-subtype distribution in patients with diabetic dyslipoproteinemia. Exp Clin Endocrinol Diabetes. 2003;111:322-324.
103. Verreth W, De Keyzer D, Pelat M, Verhamme P, Ganame J, Bielicki JK, Mertens A, Quarck R, Benhabiles N, Marguerie G, Mackness B, Mackness M, Ninio E, Herregods MC, Balligand JL, Holvoet P. Weight-loss-associated induction of peroxisome proliferator-activated receptor-alpha and peroxisome proliferator-activated receptor-gamma correlate with reduced atherosclerosis and improved cardiovascular function in obese insulin-resistant mice. Circulation. 2004;110:3259-3269.
104. Chaput E, Maubrou-Sanchez D, Bellamy FD, Edgar AD. Fenofibrate protects lipoprotein from lipid peroxidation: synergistic interaction with alpha-tocopherol. Lipids. 1999;34:497-502.
105. Halle M, Berg A, Keul J, Baumstark MW. Association between serum fibrinogen and HDL and LDL subfraction phenotypes in healthy men. Arterioscler Thromb Vasc Biol. 1996;16:144-148.
106. Inoue I, Goto S, Matsumaga T, Nakajima T, Awata T, Hokari S, Komoda T, Katayama S. The ligand/activators for peroxisome proliferator-activated receptor α (PPAR-α) and PPAR-γ increase Cu2+, Zn2+ superoxide dismutase and decrease p22phox message expression in primary endhotelial cells. Metabolism. 2001;50:3-11.
107. Schiffrin EL. Peroxisome proliferator-activated receptors and cardiovascular remodeling. Am J Physiol Heart Circ Physiol. 2005;288:1037-1043.
108. Goikoetxea MJ, Beaumont J, Diez J. Peroxisome proliferator-activated receptor alpha and hypertensive heart disease. Drugs. 2004;64:9-18.
109. Yue TL, Bao W, Jucker BM, Gu JL, Romanic AM, Brown PJ, Cui J, Thudium DT, Boyce R, Burns-Kurtis CL, Mirabile RC, Aravindhan K, Ohlstein EH. Activation of peroxisome proliferator-activated receptor-alpha protects the heart from ischemia/reperfusion injury. Circulation. 2003;108:2393-2399.
110. Iglarz M, Touyz RM, Amiri F, Lavoie MF, Diep QN, Schiffrin EL. Effect of peroxisome proliferator-activated receptor-alpha and -gamma activators on vascular remodeling in endothelin-dependent hypertension. Arterioscler Thromb Vasc Biol. 2003;23:45-51.
111. Williams JM, Zhao X, Wang MH, Imig JD, Pollock DM. Peroxisome proliferator-activated receptor-alpha activation reduces salt-dependent hypertension during chronic endothelin B receptor blockade. Hypertension. 2005;46:366-371.
112. Finck BN, Lehman JJ, Leone TC, Welch MJ, Bennett MJ, Kovacs A, Han X, Gross RW, Kozak R, Lopaschuk GD, Kelly DP. The cardiac phenotype induced by PPAR-alpha overexpression mimics that caused by diabetes mellitus. J Clin Invest. 2002;109:121-130.
113. Ye P, Li JJ, Su G, Zhang C. Effects of fenofibrate on inflammatory cytokines and blood pressure in patients with hypertriglyceridemia. Clin Chim Acta. 2005;356:229-232.