Pleiotropic effects of fenofibrate

Current Pharmaceutical Design

Volumn 15, Issue 5, 2009, Pages 517-528

  Tsimihodimos, V ^a   Liberopoulos, E ^a   Elisaf, M ^a  

^a UNIVERSITY OF IOANNINA   (Greece)

Author keywords

Angiogenesis; Cardiac remodeling; Endothelial function; Fenofibrate; Inflammation; Lipoprotein associated enzymes; Oxidative stress; Pleiotropic effects

Indexed keywords

ALANINE AMINOTRANSFERASE; ALKALINE PHOSPHATASE; ALPHA TOCOPHEROL; ARYLDIALKYLPHOSPHATASE 1; BEZAFIBRATE; C REACTIVE PROTEIN; CHOLESTEROL ESTER TRANSFER PROTEIN; CIPROFIBRATE; CYCLOSPORIN; CYTOCHROME P450; DRUG METABOLIZING ENZYME; ENDOTHELIAL NITRIC OXIDE SYNTHASE; FATTY ACID; FENOFIBRATE; FOLIC ACID; GAMMA GLUTAMYLTRANSFERASE; GLUTATHIONE PEROXIDASE; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; LOW DENSITY LIPOPROTEIN CHOLESTEROL; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; PLASMINOGEN ACTIVATOR INHIBITOR 1; SUPEROXIDE DISMUTASE; THIAZIDE DIURETIC AGENT; THROMBOPLASTIN; URIC ACID; ANTILIPEMIC AGENT; LIPOPROTEIN;

ALANINE AMINOTRANSFERASE BLOOD LEVEL; ALKALINE PHOSPHATASE BLOOD LEVEL; ANTIANGIOGENIC ACTIVITY; ANTIINFLAMMATORY ACTIVITY; ANTIOXIDANT ACTIVITY; ATHEROSCLEROSIS; BLOOD CLOT LYSIS; BLOOD PRESSURE REGULATION; CARBOHYDRATE METABOLISM; DIABETES MELLITUS; DIABETIC RETINOPATHY; DRUG ACTIVITY; DRUG BIOAVAILABILITY; DRUG CAPSULE; DRUG EFFICACY; DRUG ELIMINATION; DRUG HALF LIFE; DRUG POTENTIATION; DRUG PROTEIN BINDING; DRUG SOLUBILITY; DYSLIPIDEMIA; ENZYME ACTIVITY; FATTY ACID OXIDATION; GAMMA GLUTAMYL TRANSFERASE BLOOD LEVEL; HUMAN; HYPERTENSION; HYPERTRIGLYCERIDEMIA; LIPOPROTEIN METABOLISM; NONHUMAN; OXIDATIVE STRESS; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; TABLET FORMULATION; TRANSCRIPTION INITIATION; UPREGULATION; URIC ACID BLOOD LEVEL; ANIMAL; DISEASE COURSE; DRUG EFFECT; GENE EXPRESSION REGULATION; METABOLISM; PATHOPHYSIOLOGY;

ANIMALS; ANTILIPEMIC AGENTS; ATHEROSCLEROSIS; DISEASE PROGRESSION; GENE EXPRESSION REGULATION; HUMANS; LIPOPROTEINS; PROCETOFEN;

EID: 64749093561     PISSN: 13816128     EISSN: None     Source Type: Journal    
DOI: 10.2174/138161209787315675     Document Type: Review

References (245)

1. Keating GM, Ormrod D. Micronised fenofibrate: An updated review of its clinical efficacy in the management of dyslipidaemia. Drugs 2002; 62: 1909-44.
2. Adkins JC, Faulds U-M-icronised fenofibrate: A review of its pharmacodynamic properties and clinical efficacy in the management of dyslipidaemia. Drugs 1997; 54: 615-33.
3. Munoz A, Guichard JP, Reginault P. Micronised fenofibrate. Atherosclerosis 1994; 110(Suppl): S45-S48.
4. Tziomalos K, Athyros VG. Fenofibrate: A novel formulation (Triglide) in the treatment of lipid disorders: A review. Int J Nanomed 2006; 1: 129-47.
5. Guichard JP, Blouquin P, Qing Y. A new formulation of fenofibrate: suprabioavailable tablets. Curr Med Res Opin 2000; 16: 134-8.
6. Ramjattan BR, Callaghan DJ, Theiss U. Efficacy and tolerability of a "suprabioavailable" formulation of fenofibrate in patients with dyshpidemia: A pooled analysis of two open-label trials. Clin Ther 2002; 24: 1105-16.
7. Miller DB, Spence JD. Clinical pharmacokinetics of fibric acid derivatives (fibrates). Clin Pharmacokinet 1998; 34: 155-62.
8. Farnier M, Salko T, Isaacsohn JL, Troendle AJ, Dejager S, Gonasun L. Effects of baseline level of triglycerides on changes in lipid levels from combined fluvastatin + fibrate (bezafibrate, fenofibrate, or gemfibrozil). Am J Cardiol 2003; 92: 794-7.
9. Vega GL, Ma PT, Cater NB, Filipchuk N, Meguro S, Garcia-Garcia AB, et al. Effects of adding fenofibrate (200 mg/day) to simvastatin (10 mg/ day) in patients with combined hyperlipidemia and metabolic syndrome. Am J Cardiol 2003; 91: 956-60.
10. Grundy SM, Vega GL, Yuan Z, Battisti WP, Brady WE, Palmisano J. Effectiveness and tolerability of simvastatin plus fenofibrate for combined hyperlipidemia (the SAFARI trial). Am J Cardiol 2005; 95: 462-8.
11. Martin PD, Dane AL, Schneck DW, Warwick MJ. An open-label, randomized, three-way crossover trial of the effects of coadministration of rosuvastatin and fenofibrate on the pharmacokinetic properties of rosuvastatin and fenofibric acid in healthy male volunteers. Clin Ther 2003; 25: 459-71.
12. Corbelli JC, Bullano MF, Willey VJ, Cziraky MJ, Corbelli ME, Waugh W. Effects of gemfibrozil conversion to fenofibrate on lipids in patients on statin therapy. Am J Cardiol 2002; 90: 1388-91.
13. Prueksaritanont T, Tang C, Qiu Y, Mu L, Subramanian R, Lin JH. Effects of fibrates on metabolism of statins in human hepatocytes. Drug Metab Dispos 2002; 30: 1280-7.
14. Farnier M, Roth E, Gil-Extremera B, Mendez GF, Macdonell G, Hamlin C, et al. Efficacy and safety of the coadministration of ezetimibe/ simvastatin with fenofibrate in patients with mixed hyperlipidemia. Am Heart J 2007; 153: 335-8.
15. McKenney JM, Farnier M, Lo KW, Bays HE, Perevozkaya I, Carlson G, et al. Safety and efficacy of long-term co-administration of fenofibrate and ezetimibe in patients with mixed hyperhpidemia. J Am Coll Cardiol 2006; 47: 15 84-7.
16. Farnier M, Bortolini M, Salko T, Freudenreich MO, Isaacsohn JL, Troendle AJ, et al. Frequency of creatine kinase elevation during treatment with fluvastatin in combination with fibrates (bezafibrate, fenofibrate, or gemfibrozil). Am J Cardiol 2003; 91: 23 8-40.
17. May HT, Anderson JL, Pearson M Jensen JR, Horne BD, Lavasani F, et al. Comparison of effects of simvastatin alone versus fenofibrate alone versus simvastatin plus fenofibrate on lipoprotein subparticle profiles in diabetic patients with mixed dyslipidemia (from the Diabetes and Combined Lipid Therapy Regimen study). Am J Cardiol 2008; 101: 486-9.
18. Wierzbicki AS, Mikhailidis DP, Wray R. Drug treatment of combined hyperlipidemia. Am J Cardiovasc Drugs 2001; 1: 327-36.
19. Wierzbicki AS, Mikhailidis DP, Wray R, Schacter M, Cramb R, Simpson WG, et al. Statin-fAbrate combination: Therapy for hyperlipidemia: a review. Curr Med Res Opin 2003; 19: 155-68.
20. Kim KY, Mancano MA. Fenofibrate potentiates warfarin effects. Ann Pharmacother 2003; 37: 212-5.
21. Boissonnat P, Salen P, Guidollet J, Ferrera R, Dureau G, Ninet J, et al. The long-term effects of the lipid-lowering agent fenofibrate in hyperlipidemic heart transplant recipients. Transplantation 1994; 58: 245-7.
22. Guay DR. Micronized fenofibrate: A new fibric acid hypolipidemic agent. Ann Pharmacother 1999; 33: 1083-103.
23. Barker BJ, Goodenough RR, Falko JM. Fenofibrate monotherapy induced rhabdomyolysis. Diabetes Cate 2003; 26: 2482-3.
24. Kiortsis DN, Nikas S, Hatzidimou K, Tsianos E, Elisaf MS. Lipid-lowering drugs and serum liver enzymes: The effects of body weight and baseline enzyme levels. Fundam Clin Pharmacol 2003; 17: 491-4.
25. Florentin M, Liberopoulos EN, Mikhailidis DP, Elisaf MS. Fibrate-associated adverse effects beyond muscle and liver toxicity. Curr Pharm Des 2008; 14: 574-87.
26. Holoshitz N, Alsheikh-Ali AA, Karas RH. Relative safety of gemfibrozil and fenofibrate in the absence of concomitant cerivastatin use. Am J Cardiol 2008; 101: 95-7.
27. Broeders N, Knoop C, Antoine M, Tielemans C, Abramowicz D. Fibrate-induced increase in blood urea and creafinine: Is gemfibrozil the only innocuous agent? Nephrol Dial Transplant 2000; 15: 1993-9.
28. Tsimihodimos V, Kakafika A, Elisaf M. Fibrate treatment can increase serum creatinine levels. Nephrol Dial Transplant 2001; 16: 1301.
29. Hottelart C, El Esper N, Rose F, Achard JM, Fournier A. Fenofibrate increases creatininemia by increasing metabolic production of creatinine. Nephron 2002; 92: 536-41.
30. Tsimihodimos V, Bairaktari E, Elisaf M. Fibrate-induced increase in serum urea and creatinine levels. Nephrol Dial Transplant 2002; 17: 682.
31. Melenovsky V, Stulc T, Kozich V, Grauova B, Krijt J, Wichterle D, et al. Effect of folic acid on fenofibrate-induced elevation of homocysteine and cysteine. Am Heart J 2003; 146: 110.
32. Milionis HJ, Papakostas J, Kakafika A, Chasiotis G, Seferiadis K, Elisaf MS. Comparative effects of atorvastatin, simvastatin, and fenofibrate on serum homocysteine levels in patients with primary hyperlipidemia. J Clin Pharmacol 2003; 43: 825-30.
33. Dierkes J, Westphal S, Luley C. The effect of fibrates and other lipid-lowering drugs on plasma homocysteine levels. Expert Opin Drug Saf 2004; 3: 101-11.
34. Dierkes J, Westphal S, Luley C. Fenofibrate-induced hyperhomocysteinaemia: Clinical implications and management. Drug Saf 2003; 26: 81-91.
35. Luc G, Jacob N, Bouly M, Fruchart JC, Staels B, Giral P. Fenofibrate increases homocystinemia through a PPARalpha-mediated mechanism. J Cardiovasc Pharmacol 2004; 43: 452-3.
36. Legendre C, Causse E, Chaput E, Salvayre R, Pineau T, Edgar AD. Fenofibrate induces a selective increase of protein-bound homocysteine in rodents: A PPARalpha-mediated effect. Biochem Biophys Res Commun 2002; 295: 1052-6.
37. Genest J, Frohlich J, Steiner G. Effect of fenofibrate-mediated increase in plasma homocysteine on the progression of coronary artery disease in type 2 diabetes mellitus. Am J Cardiol 2004; 93: 848-53.
38. Willson TM, Brown PJ, Sternbach DD, Henke BR. The PPARs: From orphan receptors to drug discovery. J Med Chem 2000; 43: 527-50.
39. Schoonjans K, Staels B, Auwerx J. Role of the peroxisome proliferator-activated receptor (PPAR) in mediating the effects of fibrates and fatty acids on gene expression. J Lipid Res 1996; 37: 907-25.
40. FrucFart JC, Staels B, Duriez P. The role of fibric acids in atherosclerosis. Curr Atheroscler Rep 2001; 3: 83-92.
41. Valasek MA, Clarke SL, Repa JJ. Fenofibrate reduces intestinal cholesterol absorption via PPARalpha-dependent modulation of NPCILI expression in mouse. J Lipid Res 2007; 48: 2725-35.
42. Hahn SE, Goldberg DM. Modulation of lipoprotein-production in Hep G2 cells by fenofibrate and clofibrate. Biochem Pharmacol 1992; 43: 625-33.
43. Schoonjans K, Watanabe M, Suzuki H, Mahfoudi A, Krey G, Wahli W, et al. Induction of the acyl-coenzyme A synthetase gene by fibrates and fatty acids is mediated by a peroxisome proliferator response element in the C promoter. J Biol Chem 1995; 270: 19269-76.
44. Schoonjans K, Peinado-Onsurbe J, Lefebvre AM, Heyman RA, Briggs K Deeb S, et al. PPARalpha and PPARgamma activators direct a distinct tissue-specific transcriptional response via a PPRE in the lipoprotein lipase gene. EMBO J 1996; 15: 5336-48.
45. Haubenwallner S, Essenburg AD, Barnett BC, Pape ME, DeMattos RB, Krause BR, et al. Hypolipidemic activity of select fibrates correlates to changes in hepatic apolipoprotein C-III expression: A potential physiologic basis for their mode of action. J Lipid Res 1995; 36: 2541-51.
46. Staels B, Vu-Dac N, Kosykh VA, Saladin R, Fruchart JC, Daltongeville J, et al. Fibrates downregulate apolipoprotein C-III expression independent of induction of peroxisomal acyl coenzyme A oxidase. A potential mechanism for the hypolipidemic action of fibrates. J Clin Invest 1995; 95: 705-12.
47. Pennacchio LA, Oliver M, Hubacek JA, Cohen JC, Cox DR, Fruchart JC, et al. An apolipoprotein influencing triglycerides in humans and mice revealed by comparative sequencing. Science 2001; 294: 169-73.
48. Vu-Dac N, Gervois P, Jakel H, Nowak M, Bauge E, Dehondt H, et al. Apolipoprotein A5, a crucial determinant of plasma triglyceride levels, is highly responsive to peroxisome proliferator-activated receptor alpha activators. J Biol Chem 2003; 278: 17982-5.
49. Schultze AE, Alborn WE, Newton RK, Konrad RJ. Administration of a PPARalpha agonist increases serum apolipoprotein A-V levels and the apolipoprotein A-V/apolipoprotein C-III ratio. J Lipid Res 2005; 46: 1591-5.
50. Lai CQ Arnett DK, Corella D, Straka RJ, Tsai MY, Peacock JM, et al. Fenofibrate effect on triglyceride and postprandial response of apolipoprotein A5 variants: The GOLDN study. Arterioscler Thromb Vasc Biol 2007; 27: 1417-25.
51. Filippatos TD, Gazi IF, Liberopoulos EN, Athyros VG, Elisaf MS, Tselepis AD, et al. The effect of orlistat and fenofibrate, alone or in combination, on small dense LDL and lipoprotein-associated phospholipase A2 in obese patients with metabolic syndrome. Atherosclerosis 2007; 193: 428-37.
52. Griffin BA, Freeman DJ, Tait GW, Thomson J, Caslake MJ, Packard CJ, et al. Role of plasma triglyceride in the regulation of plasma low density lipoprotein (LDL) subfractions: Relative contribution of small, dense LDL to coronary heart disease risk. Atherosclerosis 1994; 106:241-53.
53. Guerin M, Bruckert E, Dolphin PJ, Turpin G, Chapman MJ. Fenofibrate reduces plasma cholesteryl ester transfer from HDL to VLDL and normalizes the atherogenic, dense LDL profile in combined hyperlipidemia. Arterioscler Thromb Vasc Biol 1996; 16: 763-72.
54. Gazi IF, Tsimihodimos V, Tselepis AD, Elisaf M, Mikhailidis DP. Clinical importance and therapeutic modulation of small dense low-density lipoprotein particles. Expert Opin Biol Ther 2007; 7: 53-72.
55. Vu-Dac N, Schoonjans K, Kosykh V, Dallongeville J, Fruchart JC, Staels B, et al. Fibrates increase human apolipoprotein A-II expression through activation of the peroxisome proliferator-activated receptor. J Clin Invest 1995; 96: 741-50.
56. Berthou L, Saladin R, Yaqoob P, Branellec D, Calder P, Fruchart JC, et al. Regulation of rat liver apolipoprotein A-I, apolipoprotein A-II and acyl-coenzyme A oxidase gene expression by fibrates and dietary fatty acids. Eur J Biochem 1995; 232: 179-87.
57. Duez H, Lefebvre B, Poulain P, Torra IP, Percevault F, Luc G, et al. Regulation of human apoA-I by gemfibrozil and fenofibrate through selective peroxisome proliferator-activated receptor alpha modulation. Arterioscler Thromb Vasc Biol 2005; 25: 585-91.
58. van der Hoogt CC, de Haan W, Westerterp M, Hoekstra M, Dallinga-Thie GM, Romijn JA, et al. Fenofibrate increases HDLcholesterol by reducing cholesteryl ester transfer protein expression. J Lipid Res 2007; 48: 1763-71.
59. Chinetti G, Lestavel S, Bocher V, Remaley AT, Neve B, Torra IP, et al. PPAR-alpha and PPAR-gamma activators induce cholesterol removal from human macrophage foam cells through stimulation of the ABCA1 pathway. Nat Med 2001; 7: 53-8.
60. Forcheron F, Cachefo A, Thevenon S, Pinteur C, Beylot M. Mechanisms of the triglyceride- and cholesterol-lowering effect of fenofibrate in hyperlipidemic type 2 diabetic patients. Diabetes 2002; 51: 3486-91
61. Arakawa R, Tamehiro N, Nishimaki-Mogami T, Ueda K, Yokoyama S. Fenofibric acid, an active form of fenofibrate, increases apolipoprotein A-I-mediated high-density lipoprotein biogenesis by enhancing transcription of ATP-binding cassette transporter A1 gene in a liver X receptor-dependent manner. Arterioscler Thromb Vasc Biol 2005; 25: 1193-7.
62. Hossain MA, Tsujita M, Gonzalez FJ, Yokoyama S. Effects of Fibrate Drugs on Expression of ABCA1 and HDL Biogenesis in Hepatocytes. J Cardiovasc Pharmacol 2008; 51: 258-66.
63. Chinetti G, Gbaguidi FG, Griglio S, Mallat Z, Antonucci M, Poulain P, et al. CLA-1/SR-BI is expressed in atherosclerotic lesion macrophages and regulated by activators of peroxisome proliferator- activated receptors. Circulation 2000; 101: 2411-7.
64. Nieland TJ, Shaw JT, Jaipuri FA, Maliga Z, Duffner JL, Koehler AN, et al. Influence of HDL-cholesterol-elevating drugs on the in vitro activity of the HDL receptor SR-BI. J Lipid Res 2007; 48: 1832-45.
65. Packard KA, Backes JM, Lenz TL, Wurdeman RL, Destache C, Hilleman DE. Comparison of gemfibrozil and fenofibrate in patients with dyslipidemic coronary heart disease. Pharmacotherapy 2002; 22: 1527-32.
66. Feher MD, Caslake M, Foxton J, Cox A, Packard CJ. Atherogenic lipoprotein phenotype in type 2 diabetes: Reversal with micronised fenofibrate. Diabetes Metab Res Rev 1999; 15: 395-9.
67. Krempf M, Rohmer V, Farnier M, Issa-Sayegh M, Corda C, Sirugue I, et al. Efficacy and safety of micronised fenofibrate in a randomised double-blind study comparing four doses from 200 mg to 400 mg daily with placebo in patients with hypercholesterolemia. Diabetes Metab 2000; 26: 184-91.
68. Cavallero E, Dachet C, Assadolahi F, Martin C, Navarro N, Ansquer JC, et al. Micronized fenofibrate normalizes the enhanced lipidemic response to a fat load in patients with type 2 diabetes and optimal glucose control. Atherosclerosis 2003; 166: 151-61.
69. Westphal S, Wiens L, Guttler K, Dierkes J, Luley C. Chylomicron remnants of various sizes are lowered more effectively by fenofibrate than by atorvastatin in patients with combined hyperlipidemia. Atherosclerosis 2003; 171: 369-77.
70. Ooi TC, Cousins M, Ooi DS, Nakajima K, Edwards AL. Effect of fibrates on postprandial remnant-like particles in patients with combined hyperlipidemia. Atherosclerosis 2004; 172: 375-82.
71. Bairaktari ET, Tzallas CS, Tsimihodimos VK, Liberopoulos EN, Miltiadous GA, Elisaf MS. Comparison of the efficacy of atorvastatin and micronized fenofibrate in the treatment of mixed hyperlipidemia. J Cardiovasc Risk 1999; 6: 113-6.
72. Farnier M, Bonnefous F, Debbas N, Irvine A. Comparative efficacy and safety of micronized fenofibrate and simvastatin in patients with primary type IIa or IIb hyperlipidemia. Arch Intern Med 1994; 154: 441-9.
73. Brown WV, Dujovne CA, Farquhar JW, Feldman EB, Grundy SM, Knopp RH, et al. Effects of fenofibrate on plasma lipids. Doubleblind, multicenter study in patients with type IIA or IIB hyperlipidemia. Arteriosclerosis 1986; 6: 670-8.
74. Sharpe M, Ormrod D, Jarvis B. Micronized fenofibrate in dyslipidemia: A focus on plasma high-density lipoprotein cholesterol (HDL-C) levels. Am J Cardiovasc Drugs 2002; 2: 125-32.
75. le Roux CW, Murphy E, Seed M. A retrospective assessment of the effectiveness of fenofibrate 267 mg on high-density lipoprotein cholesterol levels in patients attending a lipid clinic. Clin Ther 2002; 24: 1154-60.
76. Sasaki J, Yamamoto K, Ageta M. Effects of fenofibrate on highdensity lipoprotein particle size in patients with hyperlipidemia: A randomized, double-blind, placebo-controlled, multicenter, crossover study. Clin Ther 2002; 24: 1614-26.
77. Filippatos TD, Liberopoulos EN, Kostapanos M, Gazi IF, Papavasiliou EC, Kiortsis DN, et al. The effects of orlistat and fenofibrate, alone or in combination, on high-density lipoprotein subfractions and pre-beta1-HDL levels in obese patients with metabolic syndrome. Diabetes Obes Metab 2008; 10(6): 476-83.
78. Kontush A, Chapman MJ. Antiatherogenic small, dense HDL - guardian angel of the arterial wall? Nat Clin Pract Cardiovasc Med 2006; 3: 144-53.
79. Tsimihodimos V, Kakafika A, Tambaki AP, Bairaktari E, Chapman MJ, Elisaf M, et al. Fenofibrate induces HDL-associated PAF-AH but attenuates enzyme activity associated with apoB-containing lipoproteins. J Lipid Res 2003; 44: 927-34.
80. Caslake MJ, Packard CJ, Gaw A, Murray E, Griffin BA, Vallance BD, et al. Fenofibrate and LDL metabolic heterogeneity in hypercholesterolemia. Arterioscler Thromb 1993; 13: 702-11.
81. Shepherd J, Caslake MJ, Lorimer AR, Vallance BD, Packard CJ. Fenofibrate reduces low density lipoprotein catabolism in hypertriglyceridemic subjects. Arteriosclerosis 1985; 5: 162-8.
82. Lemieux I, Salomon H, Despres JP. 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: 442-8.
83. Lemieux I, Laperriere L, Dzavik V, Tremblay G, Bourgeois J, Despres JP. A 16-week fenofibrate treatment increases LDL particle size in type IIA dyslipidemic patients. Atherosclerosis 2002; 162: 363-71.
84. Bilz S, Wagner S, Schmitz M, Bedynek A, Keller U, Demant T. Effects of atorvastatin versus fenofibrate on apoB-100 and apoA-I kinetics in mixed hyperlipidemia. J Lipid Res 2004; 45: 174-85.
85. Watts GF, Barrett PH, Ji J, Serone AP, Chan DC, Croft KD, et al. Differential regulation of lipoprotein kinetics by atorvastatin and fenofibrate in subjects with the metabolic syndrome. Diabetes 2003; 52: 803-11.
86. Winkler K, Weltzien P, Friedrich I, Schmitz H, Nickell HH, Hauck P, et al. Qualitative effect of fenofibrate and quantitative effect of atorvastatin on LDL profile in combined hyperlipidemia with dense LDL. Exp Clin Endocrinol Diabetes 2004; 112: 241-7.
87. Hogue JC, Lamarche B, Deshaies Y, Tremblay AJ, Bergeron J, Gagne C, et al. Differential effect of fenofibrate and atorvastatin on in vivo kinetics of apolipoproteins B-100 and B-48 in subjects with type 2 diabetes mellitus with marked hypertriglyceridemia. Metabolism 2008; 57: 246-54.
88. Filippatos TD, Kiortsis DN, Liberopoulos EN, Georgoula M, Mikhailidis DP, Elisaf MS. Effect of orlistat, micronised fenofibrate and their combination on metabolic parameters in overweight and obese patients with the metabolic syndrome: The FenOrli study. Curr Med Res Opin 2005; 21: 1997-2006.
89. McKenney J, Jones M, Abby S. Safety and efficacy of colesevelam hydrochloride in combination with fenofibrate for the treatment of mixed hyperlipidemia. Curr Med Res Opin 2005; 21: 1403-12.
90. Ko HS, Kim CJ, Ryu WS. Effect of fenofibrate on lipoprotein(a) in hypertriglyceridemic patients: Impact of change in triglyceride level and liver function. J Cardiovasc Pharmacol 2005; 46: 405-11.
91. Liang B, McMaster JC, Kroeger EA, Hatch GM, Mymin D, Dembinski T, et al. The effect of fenofibrate treatment on endotheliumdependent relaxation induced by oxidative modified low density lipoprotein from hyperlipidemic patients. Mol Cell Biochem 2000; 207: 123-9.
92. Marchesi S, Lupattelli G, Lombardini R, Roscini AR, Siepi D, Vaudo G, et al. Effects of fenofibrate on endothelial function and cell adhesion molecules during post-prandial lipemia in hypertriglyceridemia. J Clin Pharm Ther 2003; 28: 419-24.
93. Huang Y, Dai G, Feng Z, Lu C, Cheng B, Wang Q, et al. Effect of micronized fenofibrate on vascular endothelial function in patients with hypertriglyceridemia. Chin Med J (Engl) 2003; 116: 1767-9.
94. Capell WH, DeSouza CA, Poirier P, Bell ML, Stauffer BL, Weil KM, et al. Short-term triglyceride lowering with fenofibrate improves vasodilator function in subjects with hypertriglyceridemia. Arterioscler Thromb Vasc Biol 2003; 23: 307-13.
95. Sebestjen M, Zegura B, Keber I. Both cerivastatin and fenofibrate improve arterial vasoreactivity in patients with combined hyperlipidaemia. J Intern Med 2002; 251: 77-85.
96. Koh KK, Han SH, Quon MJ, Yeal AJ, Shin EK. Beneficial effects of fenofibrate to improve endothelial dysfunction and raise adiponectin levels in patients with primary hypertriglyceridemia. Diabetes Care 2005; 28: 1419-24.
97. Goetze S, Eilers F, Bungenstock A, Kintscher U, Stawowy P, Blaschke F, et al. PPAR activators inhibit endothelial cell migration by targeting Akt. Biochem Biophys Res Commun 2002; 293: 1431-7.
98. Varet J, Vincent L, Mirshahi P, Pille JV, Legrand E, Opolon P, et al. Fenofibrate inhibits angiogenesis in vitro and in vivo. Cell Mol Life Sci 2003; 60: 810-9.
99. Malik J, Melenovsky V, Wichterle D, Haas T, Simek J, Ceska R, et al. Both fenofibrate and atorvastatin improve vascular reactivity in combined hyperlipidaemia (fenofibrate versus atorvastatin trial - FAT). Cardiovasc Res 2001; 52: 290-8.
100. Okayasu T, Tomizawa A, Suzuki K, Manaka K, Hattori Y. PPARalpha activators upregulate eNOS activity and inhibit cytokine- induced NF-kappaB activation through AMP-activated protein kinase activation. Life Sci 2008; 82: 884-91.
101. Murakami H, Murakami R, Kambe F, Cao X, Takahashi R, Asai T, et al. Fenofibrate activates AMPK and increases eNOS phosphorylation in HUVEC. Biochem Biophys Res Commun 2006; 341: 973-8.
102. Delerive P, Martin-Nizard F, Chinetti G, Trottein F, Fruchart JC, Najib J, 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: 394-402.
103. Kronke G, Kadl A, Ikonomu E, Bluml S, Furnkranz A, Sarembock IJ, et al. Expression of heme oxygenase-1 in human vascular cells is regulated by peroxisome proliferator-activated receptors. Arterioscler Thromb Vasc Biol 2007; 27: 1276-82.
104. De Ciuceis C, Amiri F, Iglarz M, Cohn JS, Touyz RM, Schiffrin EL. Synergistic vascular protective effects of combined low doses of PPARalpha and PPARgamma activators in angiotensin IIinduced hypertension in rats. Br J Pharmacol 2007; 151: 45-53.
105. Papaharalambus CA, Griendling KK. Basic mechanisms of oxidative stress and reactive oxygen species in cardiovascular injury. Trends Cardiovasc Med 2007; 17: 48-54.
106. Steinberg D. Low density lipoprotein oxidation and its pathobiological significance. J Biol Chem 1997; 272: 20963-6.
107. Gillotte-Taylor K, Boullier A, Witztum JL, Steinberg D, Quehenberger O. Scavenger receptor class B type I as a receptor for oxidized low density lipoprotein. J Lipid Res 2001; 42: 1474-82.
108. Mayer O, Jr., Simon J, Holubec L, Pikner R, Trefil L. Folate coadministration improves the effectiveness of fenofibrate to decrease the lipoprotein oxidation and endothelial dysfunction surrogates. Physiol Res 2006; 55: 475-81.
109. Rosenson RS. Fenofibrate reduces lipoprotein associated phospholipase A2 mass and oxidative lipids in hypertriglyceridemic subjects with the metabolic syndrome. Am Heart J 2008; 155: 499-16.
110. Rosenson RS, Wolff DA, Huskin AL, Helenowski IB, Rademaker AW. Fenofibrate therapy ameliorates fasting and postprandial lipoproteinemia, oxidative stress, and the inflammatory response in subjects with hypertriglyceridemia and the metabolic syndrome. Diabetes Care 2007; 30: 1945-51.
111. Arca M, Natoli S, Micheletta F, Riggi S, Di Angelantonio E, Montali A, et al. Increased plasma levels of oxysterols, in vivo markers of oxidative stress, in patients with familial combined hyperlipidemia: Reduction during atorvastatin and fenofibrate therapy. Free Radic Biol Med 2007; 42: 698-705.
112. Engelen W, Keenoy B, Vertommen J, De L, I, Van Gaal L. Effects of micronized fenofibrate and vitamin E on in vitro oxidation of lipoproteins in patients with type 1 diabetes mellitus. Diabetes Metab 2005; 31: 197-204.
113. Tkac I, Molcanyiova A, Javorsky M, Kozarova M. Fenofibrate treatment reduces circulating conjugated diene level and increases glutathione peroxidase activity. Pharmacol Res 2006; 53: 261-4.
114. Hogue JC, Lamarche B, Tremblay AJ, Bergeron J, Gagne C, Couture P. Differential effect of atorvastatin and fenofibrate on plasma oxidized low-density lipoprotein, inflammation markers, and cell adhesion molecules in patients with type 2 diabetes mellitus. Metabolism 2008; 57: 380-6.
115. Inoue I, Goto S, Matsunaga T, Nakajima T, Awata T, Hokari S, 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: 3-11.
116. Ross R. Atherosclerosis - an inflammatory disease. N Engl J Med 1999; 340: 115-26.
117. Athyros VG, Kakafika AI, Karagiannis A, Mikhailidis DP. Do we need to consider inflammatory markers when we treat atherosclerotic disease? Atherosclerosis 2008; 200(1): 1-12.
118. Libby P, Ridker PM. Inflammation and atherosclerosis: Role of C-reactive protein in risk assessment. Am J Med 2004; 116(Suppl 6A): 9S-16S.
119. Tsimihodimos V, Kostoula A, Kakafika A, Bairaktari E, Tselepis AD, Mikhailidis DP, et al. Effect of fenofibrate on serum inflammatory markers in patients with high triglyceride values. J Cardiovasc Pharmacol Ther 2004; 9: 27-33.
120. Muhlestein JB, May HT, Jensen JR, Horne BD, Lanman RB, Lavasani F, 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: 396-401.
121. Staels B, Koenig W, Habib A, Merval R, Lebret M, Torra IP, et al. Activation of human aortic smooth-muscle cells is inhibited by PPARalpha but not by PPARgamma activators. Nature 1998; 393: 790-3.
122. Rosenson RS, Huskin AL, Wolff DA, Helenowski IB, Rademaker AW. Fenofibrate reduces fasting and postprandial inflammatory responses among hypertriglyceridemia patients with the metabolic syndrome. Atherosclerosis 2008;
123. Shen J, Arnett DK, Parnell LD, Peacock JM, Lai CQ, Hixson JE, et al. Association of common C-reactive protein (CRP) gene polymorphisms with baseline plasma CRP levels and fenofibrate response: The GOLDN study. Diabetes Care 2008; 31: 910-5.
124. Murai T, Yamada T, Miida T, Arai K, Endo N, Hanyu T. Fenofibrate inhibits reactive amyloidosis in mice. Arthritis Rheum 2002; 46: 1683-8.
125. Gervois P, Kleemann R, Pilon A, Percevault F, Koenig W, Staels B, et al. Global suppression of IL-6-induced acute phase response gene expression after chronic in vivo treatment with the peroxisome proliferator-activated receptor-alpha activator fenofibrate. J Biol Chem 2004; 279: 16154-60.
126. Okopien B, Krysiak R, Kowalski J, Madej A, Belowski D, Zielinski M, et al. The effect of statins and fibrates on interferon-gamma and interleukin-2 release in patients with primary type II dyslipidemia. Atherosclerosis 2004; 176: 327-35.
127. Sebestjen M, Keber I, Zegura B, Simcic S, Bozic M, Fressart MM, et al. Statin and fibrate treatment of combined hyperlipidemia: The effects on some novel risk factors. Thromb Haemost 2004; 92: 1129-35
128. Okopien B, Krysiak R, Kowalski J, Madej A, Belowski D, Zielinski M, et al. Monocyte release of tumor necrosis factor-alpha and interleukin-1beta in primary type IIa and IIb dyslipidemic patients treated with statins or fibrates. J Cardiovasc Pharmacol 2005; 46: 377-86.
129. Okopien B, Huzarska M, Kulach A, Stachura-Kulach A, Madej A, Belowski D, et al. Hypolipidemic drugs affect monocyte IL-1beta gene expression and release in patients with IIa and IIb dyslipidemia. J Cardiovasc Pharmacol 2005; 45: 160-4.
130. Kowalski J, Okopien B, Madej A, Zielinski M, Belowski D, Kalina Z, et al. Effects of atorvastatin, simvastatin, and fenofibrate therapy on monocyte chemoattractant protein-1 secretion in patients with hyperlipidemia. Eur J Clin Pharmacol 2003; 59: 189-93.
131. Empen K, Frost RJ, Geiss HC, Otto C, Parhofer KG. Differential effects of fenofibrate versus atorvastatin on the concentrations of E-selectin and vascular cellular adhesion molecule-1 in patients with type 2 diabetes mellitus and mixed hyperlipoproteinemia: A randomized cross-over trial. Cardiovasc Diabetol 2003; 2: 17.
132. Undas A, Celinska-Lowenhoff M, Domagala TB, Iwaniec T, Dropinski J, Lowenhoff T, et al. Early antithrombotic and antiinflammatory effects of simvastatin versus fenofibrate in patients with hypercholesterolemia. Thromb Haemost 2005; 94: 193-9.
133. Dragomir E, Tircol M, Manduteanu I, Voinea M, Simionescu M. Aspirin and PPAR-alpha activators inhibit monocyte chemoattractant protein-1 expression induced by high glucose concentration in human endothelial cells. Vascul Pharmacol 2006; 44: 440-9.
134. Shu H, Wong B, Zhou G, Li Y, Berger J, Woods JW, et al. Activation of PPARalpha or gamma reduces secretion of matrix metalloproteinase 9 but not interleukin 8 from human monocytic THP-1 cells. Biochem Biophys Res Commun 2000; 267: 345-9.
135. Delerive P, Fruchart JC, Staels B. Peroxisome proliferatoractivated receptors in inflammation control. J Endocrinol 2001; 169: 453-9.
136. Libby P, Plutzky J. Inflammation in diabetes mellitus: Role of peroxisome proliferator-activated receptor-alpha and peroxisome proliferator-activated receptor-gamma agonists. Am J Cardiol 2007; 99: 27B-40B.
137. Tselepis AD, John CM. Inflammation, bioactive lipids and atherosclerosis: Potential roles of a lipoprotein-associated phospholipase A2, platelet activating factor-acetylhydrolase. Atheroscler Suppl 2002; 3: 57-68.
138. Matsumoto T, Kobayashi T, Kamata K. Role of lysophosphatidylcholine (LPC) in atherosclerosis. Curr Med Chem 2007; 14: 3209-20.
139. MacPhee CH, Moores KE, Boyd HF, Dhanak D, Ife RJ, Leach CA, et al. Lipoprotein-associated phospholipase A2, platelet-activating factor acetylhydrolase, generates two bioactive products during the oxidation of low-density lipoprotein: Use of a novel inhibitor. Biochem J 1999; 338 (Pt 2): 479-87.
140. Robins SJ, Collins D, Nelson JJ, Bloomfield HE, Asztalos BF. Cardiovascular Events With Increased Lipoprotein-Associated Phospholipase A2 and Low High-Density Lipoprotein-Cholesterol. The Veterans Affairs HDL Intervention Trial. Arterioscler Thromb Vasc Biol 2008; 28(6): 1172-8.
141. Daniels LB, Laughlin GA, Sarno MJ, Bettencourt R, Wolfert RL, Barrett-Connor E. Lipoprotein-associated phospholipase A2 is an independent predictor of incident coronary heart disease in an apparently healthy older population: The Rancho Bernardo Study. J Am Coll Cardiol 2008; 51: 913-9.
142. Sabatine MS, Morrow DA, O'Donoghue M, Jablonksi KA, Rice MM, Solomon S, et al. Prognostic utility of lipoprotein-associated phospholipase A2 for cardiovascular outcomes in patients with stable coronary artery disease. Arterioscler Thromb Vasc Biol 2007; 27: 2463-9.
143. Winkler K, Hoffmann MM, Winkelmann BR, Friedrich I, Schafer G, Seelhorst U, et al. Lipoprotein-associated phospholipase A2 predicts 5-year cardiac mortality independently of established risk factors and adds prognostic information in patients with low and medium high-sensitivity C-reactive protein (the Ludwigshafen risk and cardiovascular health study). Clin Chem 2007; 53: 1440-7.
144. Saougos VG, Tambaki AP, Kalogirou M, Kostapanos M, Gazi IF, Wolfert RL, et al. Differential effect of hypolipidemic drugs on lipoprotein-associated phospholipase A2. Arterioscler Thromb Vasc Biol 2007; 27: 2236-43.
145. Mackness MI, Durrington PN, Mackness B. The role of paraoxonase 1 activity in cardiovascular disease: Potential for therapeutic intervention. Am J Cardiovasc Drugs 2004; 4: 211-7.
146. Watson AD, Berliner JA, Hama SY, La Du BN, Faull KF, Fogelman AM, et al. Protective effect of high density lipoprotein associated paraoxonase. Inhibition of the biological activity of minimally oxidized low density lipoprotein. J Clin Invest 1995; 96: 2882-91.
147. Aviram M, Hardak E, Vaya J, Mahmood S, Milo S, Hoffman A, et al. Human serum paraoxonases (PON1) Q and R selectively decrease lipid peroxides in human coronary and carotid atherosclerotic lesions: PON1 esterase and peroxidase-like activities. Circulation 2000; 101: 2510-7.
148. Gouedard C, Koum-Besson N, Barouki R, Morel Y. Opposite regulation of the human paraoxonase-1 gene PON-1 by fenofibrate and statins. Mol Pharmacol 2003; 63: 945-56.
149. Phuntuwate W, Suthisisang C, Koanantakul B, Chaloeiphap P, Mackness B, Mackness M. Effect of fenofibrate therapy on paraoxonase1 status in patients with low HDL-C levels. Atherosclerosis 2008; 196: 122-8.
150. Paragh G, Seres I, Harangi M, Balogh Z, Illyes L, Boda J, et al. The effect of micronised fenofibrate on paraoxonase activity in patients with coronary heart disease. Diabetes Metab 2003; 29: 613-8.
151. Barter PJ, Kastelein JJ. Targeting cholesteryl ester transfer protein for the prevention and management of cardiovascular disease. J Am Coll Cardiol 2006; 47: 492-9.
152. Guerin M, Bruckert E, Dolphin PJ, Chapman MJ. Absence of cholesteryl ester transfer protein-mediated cholesteryl ester mass transfer from high-density lipoprotein to low-density lipoprotein particles is a major feature of combined hyperlipidaemia. Eur J Clin Invest 1996; 26: 485-94.
153. Athyros VG, Papageorgiou AA, Athyrou VV, Demitriadis DS, Kontopoulos AG. Atorvastatin and micronized fenofibrate alone and in combination in type 2 diabetes with combined hyperlipidemia. Diabetes Care 2002; 25: 1198-202.
154. Branchi A, Rovellini A, Sommariva D, Gugliandolo AG, Fasoli A. Effect of three fibrate derivatives and of two HMG-CoA reductase inhibitors on plasma fibrinogen level in patients with primary hypercholesterolemia. Thromb Haemost 1993; 70: 241-3.
155. Frost RJ, Otto C, Geiss HC, Schwandt P, Parhofer KG. Effects of atorvastatin versus fenofibrate on lipoprotein profiles, low-density lipoprotein subfraction distribution, and hemorheologic parameters in type 2 diabetes mellitus with mixed hyperlipoproteinemia. Am J Cardiol 2001; 87: 44-8.
156. Genest J, Jr., 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: 164-72.
157. Kockx M, Gervois PP, Poulain P, Derudas B, Peters JM, Gonzalez FJ, et al. Fibrates suppress fibrinogen gene expression in rodents via activation of the peroxisome proliferator-activated receptor-alpha. Blood 1999; 93: 2991-8.
158. Haak T, Haak E, Kusterer K, Weber A, Kohleisen M, Usadel KH. Fenofibrate improves microcirculation in patients with hyperlipidemia. Eur J Med Res 1998; 3: 50-4.
159. Okopien B, Krysiak R, Herman ZS. Effects of short-term fenofibrate treatment on circulating markers of inflammation and hemostasis in patients with impaired glucose tolerance. J Clin Endocrinol Metab 2006; 91: 1770-8.
160. Okopien B, Haberka M, Madej A, Belowski D, Labuzek K, Krysiak R, et al. Extralipid effects of micronized fenofibrate in dyslipidemic patients. Pharmacol Rep 2006; 58: 729-35.
161. Kilicarslan A, Yavuz B, Guven GS, Atalar E, Sahiner L, Beyazit Y, et al. Fenofibrate improves endothelial function and decreases thrombin-activatable fibrinolysis inhibitor concentration in metabolic syndrome. Blood Coagul Fibrinolysis 2008; 19: 310-4.
162. Mann KG, van't Veer C, Cawthern K, Butenas S. The role of the tissue factor pathway in initiation of coagulation. Blood Coagul Fibrinolysis 1998; 9(Suppl 1): S3-S7.
163. Neve BP, Corseaux D, Chinetti G, Zawadzki C, Fruchart JC, Duriez P, et al. PPARalpha agonists inhibit tissue factor expression in human monocytes and macrophages. Circulation 2001; 103: 207-12.
164. Marx N, Mackman N, Schonbeck U, Yilmaz N, Hombach V, Libby P, et al. PPARalpha activators inhibit tissue factor expression and activity in human monocytes. Circulation 2001; 103: 213-9.
165. Golledge J, Mangan S, Clancy P. Effects of peroxisome proliferator-activated receptor ligands in modulating tissue factor and tissue factor pathway inhibitor in acutely symptomatic carotid atheromas. Stroke 2007; 38: 1501-8.
166. Mangan S, Clancy P, Golledge J. Modulation of endothelial cell thrombomodulin by PPAR ligands - Variation according to environment. Thromb Res 2008; 121: 827-34.
167. Vaughan DE. PAI-1 and atherothrombosis. J Thromb Haemost 2005; 3: 1879-83.
168. Kockx M, Princen HM, Kooistra T. Fibrate-modulated expression, of fibrinogen, plasminogen activator inhibitor-1 and apolipoprotein A-I in cultured cynomolgus monkey hepatocytes - role of the peroxisome proliferator-activated receptor-alpha. Thromb Haemost 1998; 80: 942-8
169. Nilsson L, Takemura T, Eriksson P, Hamsten A. Effects of fibrate compounds on expression of plasminogen activator inhibitor-1 by cultured endothelial cells. Arterioscler Thromb Vasc Biol 1999; 19: 1577-81.
170. Chen J, Ye P, Liu YX, Sheng L, Han CG, He YL. Inhibition of plasminogen activator inhibitor type-1 expression in HepG2 cells by fenofibrate may be associated with Smad signaling. Clin Chim Acta 2008; 387: 18-23.
171. Okopien B, Cwalina L, Lebek M, Kowalski J, Zielinski M, Wisniewska-Wanat M, et al. Effects of fibrates on plasma prothrombotic, activity in patients with type IIb dyslipidemia. Int J Clin Pharmacol Ther 2001; 39: 551-7.
172. Mathur S, Barradas MA, Mikhailidis DP, Dandona P. The effect of a slow release formulation of bezafibrate on lipids, glucose homeostasis, platelets and fibrinogen in type II diabetics: A pilot study. Diabetes Res 1990; 14: 133-8.
173. Milionis HJ, Elisaf MS, Mikhailidis DP. The effects of lipid-regulating therapy on haemostatic parameters. Curr Pharm Des 2003; 9: 2425-43.
174. Keech A, Simes RJ, Barter P, Best J, Scott R, Taskinen MR, 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: 1849-61.
175. Reaven GM. The insulin resistance syndrome. Curr Atheroscler Rep 2003; 5: 364-71.
176. Guerre-Millo M, Gervois P, Raspe E, Madsen L, Poulain P, Derudas B, et al. Peroxisome proliferator-activated receptor alpha activators improve insulin sensitivity and reduce adiposity. J Biol Chem 2000; 275: 16638-42.
177. Nagai Y, Nishio Y, Nakamura T, Maegawa H, Kikkawa R, Kashiwagi A. Amelioration of high fructose-induced metabolic derangements by activation of PPARalpha. Am J Physiol Endocrinol Metab 2002; 282: E1180-E1190.
178. Choi KC, Ryu OH, Lee KW, Kim HY, Seo JA, Kim SG, et al. Effect of PPAR-alpha and -gamma agonist on the expression of visfatin, adiponectin, and TNF-alpha in visceral fat of OLETF rats. Biochem Biophys Res Commun 2005; 336: 747-53.
179. Xie W, Nie Y, Du L, Zhang Y, Cai G. Preventive effects of fenofibrate on insulin resistance, hyperglycaemia, visceral fat accumulation in NIH mice induced by small-dose streptozotocin and lard. Pharmacol Res 2007; 55: 392-9.
180. Idzior-Walus B, Sieradzki J, Rostworowski W, Zdzienicka A, Kawalec E, Wojcik J, et al. Effects of comicronised fenofibrate on lipid and insulin sensitivity in patients with polymetabolic syndrome X. Eur J Clin Invest 2000; 30: 871-8.
181. Furuhashi M, Ura N, Murakami H, Hyakukoku M, Yamaguchi K, Higashiura K, et al. Fenofibrate improves insulin sensitivity in connection with intramuscular lipid content, muscle fatty acid-binding protein, and beta-oxidation in skeletal muscle. J Endocrinol 2002; 174: 321-9.
182. Koh EH, Lee WJ, Kim MS, Park JY, Lee IK, Lee KU. Intracellular Fatty Acid metabolism in skeletal muscle and insulin resistance. Curr Diabetes Rev 2005; 1: 331-6.
183. Hiuge A, Tenenbaum A, Maeda N, Benderly M, Kumada M, Fisman EZ, et al. Effects of peroxisome proliferator-activated receptor ligands, bezafibrate and fenofibrate, on adiponectin level. Arterioscler Thromb Vasc Biol 2007; 27: 635-41.
184. Nieuwdorp M, Stroes ES, Kastelein JJ. Normalization of metabolic syndrome using fenofibrate, metformin or their combination. Diabetes Obes Metab 2007; 9: 869-78.
185. Wysocki J, Belowski D, Kalina M, Kochanski L, Okopien B, Kalina Z. Effects of micronized fenofibrate on insulin resistance in patients with metabolic syndrome. Int J Clin Pharmacol Ther 2004; 42: 212-7.
186. Anderlova K, Dolezalova R, Housova J, Bosanska L, Haluzikova D, Kremen J, et al. Influence of PPAR-alpha agonist fenofibrate on insulin sensitivity and selected adipose tissue-derived hormones in obese women with type 2 diabetes. Physiol Res 2007; 56: 579-86.
187. Bajaj M, Suraamornkul S, Hardies LJ, Glass L, Musi N, DeFronzo RA. Effects of peroxisome proliferator-activated receptor (PPAR)-alpha and PPAR-gamma agonists on glucose and lipid metabolism in patients with type 2 diabetes mellitus. Diabetologia 2007; 50: 1723-31.
188. Subramanian S, DeRosa MA, Bernal-Mizrachi C, Laffely N, Cade WT, Yarasheski KE, et al. PPARalpha activation elevates blood pressure and does not correct glucocorticoid-induced insulin resistance in humans. Am J Physiol Endocrinol Metab 2006; 291: E1365-E1371.
189. Shatara RK, Quest DW, Wilson TW. Fenofibrate lowers blood pressure in two genetic models of hypertension. Can J Physiol Pharmacol 2000; 78: 367-71.
190. Zhao X, Li LY. PPAR-Alpha Agonist Fenofibrate Induces Renal CYP Enzymes and Reduces Blood Pressure and Glomerular Hypertrophy in Zucker Diabetic Fatty Rats. Am J Nephrol 2008; 28: 598-606.
191. Vera T, Taylor M, Bohman Q, Flasch A, Roman RJ, Stec DE. Fenofibrate prevents the development of angiotensin II-dependent hypertension in mice. Hypertension 2005; 45: 730-5.
192. Roman RJ. P-450 metabolites of arachidonic acid in the control of cardiovascular function. Physiol Rev 2002; 82: 131-85.
193. Dos Santos EA, Dahly-Vernon AJ, Hoagland KM, Roman RJ. Inhibition of the formation of EETs and 20-HETE with 1-aminobenzotriazole attenuates pressure natriuresis. Am J Physiol Regul Integr Comp Physiol 2004; 287: R58-R68.
194. Maier KG, Roman RJ. Cytochrome P450 metabolites of arachidonic acid in the control of renal function. Curr Opin Nephrol Hypertens 2001; 10: 81-7.
195. Ansquer JC, Foucher C, Rattier S, Taskinen MR, Steiner G. Fenofibrate reduces progression to microalbuminuria over 3 years in a placebo-controlled study in type 2 diabetes: Results from the Diabetes Atherosclerosis Intervention Study (DAIS). Am J Kidney Dis 2005; 45: 485-93.
196. Haider AW, Larson MG, Franklin SS, Levy D. Systolic blood pressure, diastolic blood pressure, and pulse pressure as predictors of risk for congestive heart failure in the Framingham Heart Study. Ann Intern Med 2003; 138: 10-6.
197. Levy D, Anderson KM, Savage DD, Kannel WB, Christiansen JC, Castelli WP. Echocardiographically detected left ventricular hypertrophy: Prevalence and risk factors. The Framingham Heart Study. Ann Intern Med 1988; 108: 7-13.
198. Lebrasseur NK, Duhaney TA, De Silva DS, Cui L, Ip PC, Joseph L, et al. Effects of fenofibrate on cardiac remodeling in aldosterone-induced hypertension. Hypertension 2007; 50: 489-96.
199. Li R, Zheng W, Pi R, Gao J, Zhang H, Wang P, et al. Activation of peroxisome proliferator-activated receptor-alpha prevents glycogen synthase 3beta phosphorylation and inhibits cardiac hypertrophy. FEBS Lett 2007; 581: 3311-6.
200. Iglarz M, Touyz RM, Viel EC, Paradis P, Amiri F, Diep QN, et al. Peroxisome proliferator-activated receptor-alpha and receptor-gamma activators prevent cardiac fibrosis in mineralocorticoid-dependent hypertension. Hypertension 2003; 42: 737-43.
201. Brigadeau F, Gele P, Wibaux M, Marquie C, Martin-Nizard F, Torpier G, et al. The PPARalpha activator fenofibrate slows down the progression of the left ventricular dysfunction in porcine tachycardia-induced cardiomyopathy. J Cardiovasc Pharmacol 2007; 49: 408-15.
202. Ogata T, Miyauchi T, Irukayama-Tomobe Y, Takanashi M, Goto K, Yamaguchi I. The Peroxisome Proliferator-activated Receptor alpha Activator Fenofibrate Inhibits Endothelin-1-induced Cardiac Fibroblast Proliferation. J Cardiovasc Pharmacol 2004; 44(Suppl 1): S279-S282.
203. Ogata T, Miyauchi T, Sakai S, Irukayama-Tomobe Y, Goto K, Yamaguchi I. Stimulation of peroxisome-proliferator-activated receptor alpha (PPAR alpha) attenuates cardiac fibrosis and endothelin-1 production in pressure-overloaded rat hearts. Clin Sci (Lond) 2002; 103(Suppl 48): 284S-8S.
204. Irukayama-Tomobe Y, Miyauchi T, Sakai S, Kasuya Y, Ogata T, Takanashi M, et al. Endothelin-1-induced cardiac hypertrophy is inhibited by activation of peroxisome proliferator-activated receptor-alpha partly via blockade of c-Jun NH2-terminal kinase pathway. Circulation 2004; 109: 904-10.
205. Ogata T, Miyauchi T, Sakai S, Takanashi M, Irukayama-Tomobe Y, Yamaguchi I. Myocardial fibrosis and diastolic dysfunction in deoxycorticosterone acetate-salt hypertensive rats is ameliorated by the peroxisome proliferator-activated receptor-alpha activator feno-fibrate, partly by suppressing inflammatory responses associated with the nuclear factor-kappa-B pathway. J Am Coll Cardiol 2004; 43: 1481-8.
206. Duhaney TA, Cui L, Rude MK, Lebrasseur NK, Ngoy S, De Silva DS, et al. Peroxisome proliferator-activated receptor alpha-independent actions of fenofibrate exacerbates left ventricular dilation and fibrosis in chronic pressure overload. Hypertension 2007; 49: 1084-94.
207. Keech AC, Mitchell P, Summanen PA, O'Day J, Davis TM, Moffitt MS, et al. Effect of fenofibrate on the need for laser treatment for diabetic retinopathy (FIELD study): A randomised controlled trial. Lancet 2007; 370: 1687-97.
208. Tanaka T, Kohno H, Yoshitani S, Takashima S, Okumura A, Murakami A, et al. Ligands for peroxisome proliferator-activated receptors alpha and gamma inhibit chemically induced colitis and formation of aberrant crypt foci in rats. Cancer Res 2001; 61: 2424-8.
209. Maggiora M, Bologna M, Ceru MP, Possati L, Angelucci A, Cimini A, et al. An overview of the effect of linoleic and conjugated-linoleic acids on the growth of several human tumor cell lines. Int J Cancer 2004; 112: 909-19.
210. Saidi SA, Holland CM, Charnock-Jones DS, Smith SK. In vitro and in vivo effects of the PPAR-alpha agonists fenofibrate and retinoic acid in endometrial cancer. Mol Cancer 2006; 5: 13.
211. Thuillier P, Anchiraico GJ, Nickel KP, Maldve RE, Gimenez-Conti I, Muga SJ, et al. Activators of peroxisome proliferator-activated receptor-alpha partially inhibit mouse skin tumor promotion. Mol Carcinog 2000; 29: 134-42.
212. Grabacka M, Placha W, Plonka PM, Pajak S, Urbanska K, Laidler P, et al. Inhibition of melanoma metastases by fenofibrate. Arch Dermatol Res 2004; 296: 54-8.
213. Grabacka M, Plonka PM, Urbanska K, Reiss K. Peroxisome proliferator-activated receptor alpha activation decreases metastatic potential of melanoma cells in vitro via down-regulation of Akt. Clin Cancer Res 2006; 12: 3028-36.
214. Dellavalle RP, Nicholas MK, Schilling LM. Melanoma chemoprevention: A role for statins or fibrates? Am J Ther 2003; 10: 203-10.
215. Talpur R, Ward S, Apisarnthanarax N, Breuer-Mcham J, Duvic M. Optimizing bexarotene therapy for cutaneous T-cell lymphoma. J Am Acad Dermatol 2002; 47: 672-84.
216. Panigrahy D, Kaipainen A, Huang S, Butterfield CE, Barnes CM, Fannon M, et al. PPARalpha agonist fenofibrate suppresses tumor growth through direct and indirect angiogenesis inhibition. Proc Natl Acad Sci USA 2008; 105: 985-90.
217. Kasai T, Miyauchi K, Yokoyama T, Aihara K, Daida H. Efficacy of peroxisome proliferative activated receptor (PPAR)-alpha ligands, fenofibrate, on intimal hyperplasia and constrictive remodeling after coronary angioplasty in porcine models. Atherosclerosis 2006; 188: 274-80.
218. Lippi G, Montagnana M, Franchini M, Favaloro EJ, Targher G. The paradoxical relationship between serum uric acid and cardiovascular disease. Clin Chim Acta 2008; 392: 1-7.
219. Puig JG, Martinez MA. Hyperuricemia, gout and the metabolic syndrome. Curr Opin Rheumatol 2008; 20: 187-91.
220. Liamis G, Bairaktari ET, Elisaf MS. Effect of fenofibrate on serum uric acid levels. Am J Kidney Dis 1999; 34: 594.
221. Daskalopoulou SS, Tzovaras V, Mikhailidis DP, Elisaf M. Effect on serum uric acid levels of drugs prescribed for indications other than treating hyperuricaemia. Curr Pharm Des 2005; 11: 4161-75.
222. Achimastos A, Liberopoulos E, Nikas S, Bairaktari E, Miltiadous G, Tsimihodimos V, et al. The effects of the addition of micronised fenofibrate on uric acid metabolism in patients receiving indapamide. Curr Med Res Opin 2002; 18: 59-63.
223. Elisaf M, Tsimichodimos V, Bairaktari E, Siamopoulos KC. Effect of micronized fenofibrate and losartan combination on uric acid metabolism in hypertensive patients with hyperuricemia. J Cardiovasc Pharmacol 1999; 34: 60-3.
224. Milionis HJ, Elisaf MS. Management of hypertension and dyslipidaemia in patients presenting with hyperuricaemia: Case histories. Curr Med Res Opin 2000; 16: 164-70.
225. Takahashi S, Moriwaki Y, Yamamoto T, Tsutsumi Z, Ka T, Fukuchi M. Effects of combination treatment using anti-hyperuricaemic agents with fenofibrate and/or losartan on uric acid metabolism. Ann Rheum Dis 2003; 62: 572-5.
226. Yamamoto T, Moriwaki Y, Takahashi S, Tsutsumi Z, Hada T. Effect of fenofibrate on plasma concentration and urinary excretion of purine bases and oxypurinol. J Rheumatol 2001; 28: 2294-7.
227. Lee YH, Lee CH, Lee J. Effect of fenofibrate in combination with urate lowering agents in patients with gout. Korean J Intern Med 2006; 21: 89-93.
228. Feher MD, Hepburn AL, Hogarth MB, Ball SG, Kaye SA. Fenofibrate enhances urate reduction in men treated with allopurinol for hyperuricaemia and gout. Rheumatology (Oxford) 2003; 42: 321-5.
229. Takahashi S, Inokuchi T, Kobayashi T, Ka T, Tsutsumi Z, Moriwaki Y, et al. Relationship between insulin resistance and low urinary pH in patients with gout, and effects of PPARalpha agonists on urine pH. Horm Metab Res 2007; 39: 511-4.
230. Sakhaee K, Maalouf NM. Metabolic syndrome and uric acid nephrolithiasis. Semin Nephrol 2008; 28: 174-80.
231. Mikhailidis DP, Ganotakis ES, Spyropoulos KA, Jagroop IA, Byrne DJ, Winder AF. Prothrombotic and lipoprotein variables in patients attending a cardiovascular risk management clinic: Response to ciprofibrate or lifestyle advice. Int Angiol 1998; 17: 225-33.
232. Papadakis JA, Ganotakis ES, Jagroop IA, Winder AF, Mikhailidis DP. Statin + fibrate combination therapy fluvastatin with bezafibrate or ciprofibrate in high risk patients with vascular disease. Int J Cardiol 1999; 69: 237-44.
233. Steinmetz J, Morin C, Panek E, Siest G, Drouin P. Biological variations in hyperlipidemic children and adolescents treated with fenofibrate. Clin Chim Acta 1981; 112: 43.
234. Day AP, Feher MD, Chopra R, Mayne PD. The effect of bezafibrate treatment on serum alkaline phosphatase isoenzyme activities. Metabolism 1993; 42: 839-42.
235. Ganotakis E, Tsimihodimos V, Bairaktari E, Rizos E, Athyros V, Seferiades C, et al. Effects of various fibrates on serum alkaline phosphatase activity. Atherosclerosis 2002; 165: 187-8.
236. Post SM, Duez H, Gervois PP, Staels B, Kuipers F, Princen HM. Fibrates suppress bile acid synthesis via peroxisome proliferator-activated receptor-alpha-mediated downregulation of cholesterol 7alpha-hydroxylase and sterol 27-hydroxylase expression. Arterioscler Thromb Vasc Biol 2001; 21: 1840-5.
237. Cindoruk M, Kerem M, Karakan T, Salman B, Akin O, Alper M, et al. Peroxisome proliferators-activated alpha agonist treatment ameliorates hepatic damage in rats with obstructive jaundice: An experimental study. BMC Gastroenterol 2007; 7: 44.
238. Marchesini G, Bugianesi E, Forlani G, Cerrelli F, Lenzi M, Manini R, et al. Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology 2003; 37: 917-23.
239. Seo YS, Kim JH, Jo NY, Choi KM, Baik SH, Park JJ, et al. PPAR agonists treatment is effective in a nonalcoholic fatty liver disease animal model by modulating fatty-acid metabolic enzymes. J Gastroenterol Hepatol 2008; 23: 102-9.
240. Shiri-Sverdlov R, Wouters K, van Gorp PJ, Gijbels MJ, Noel B, Buffat L, et al. Early diet-induced non-alcoholic steatohepatitis in APOE2 knock-in mice and its prevention by fibrates. J Hepatol 2006; 44: 732-41.
241. Harano Y, Yasui K, Toyama T, Nakajima T, Mitsuyoshi H, Mimani M, et al. Fenofibrate, a peroxisome proliferator-activated receptor alpha agonist, reduces hepatic steatosis and lipid peroxidation in fatty liver Shionogi mice with hereditary fatty liver. Liver Int 2006; 26: 613-20.
242. Fernandez-Miranda C, Perez-Carreras M, Colina F, Lopez-Alonso G, Vargas C, Solis-Herruzo JA. A pilot trial of fenofibrate for the treatment of non-alcoholic fatty liver disease. Dig Liver Dis 2008; 40: 200-5.
243. Jandeleit-Dahm K, Cooper ME. The role of AGEs in cardiovascular disease. Curr Pharm Des 2008; 14(10): 979-86.
244. Lu X, Lu D, Scully MF, Kakkar VV. The role of integrin-mediated cell adhesion in atherosclerosis: Pathophysiology and clinical opportunities. Curr Pharm Des 2008; 14(22): 2140-58.
245. Virdis A, Ghiadoni L, Versari D, Giannarelli C, Salvetti A, Taddei S. Endothelial function assessment in complicated hypertension. Curr Pharm Des 2008; 14(18): 1761-70.