Significance of peroxisome proliferator-activated receptors in the cardiovascular system in health and disease

Pharmacology and Therapeutics

Volumn 122, Issue 3, 2009, Pages 246-263

  Robinson, Emma ^a   Grieve, David J ^a  

^a QUEEN'S UNIVERSITY BELFAST   (United Kingdom)

Author keywords

Atherosclerosis; Cardiovascular disease (CVD); Heart; Hypertension; Hypertrophy; Peroxisome proliferator activated receptor (PPAR)

Indexed keywords

2 CHLORO 5 NITROBENZANILIDE; 2,4 THIAZOLIDINEDIONE DERIVATIVE; 4 [4 [3 (4 ACETYL 3 HYDROXY 2 PROPYLPHENOXY)PROPOXY]PHENOXY]ACETIC ACID; [4 [2 (3 FLUORO 4 TRIFLUOROMETHYLPHENYL) 4 METHYL 5 THIAZOLYLMETHYLTHIO] 2 METHYLPHENOXY]ACETIC ACID; BEZAFIBRATE; CIGLITAZONE; CLOFIBRATE; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; ENDOTHELIN 1; FENOFIBRATE; FIBRIC ACID DERIVATIVE; GELATINASE B; GEMFIBROZIL; HIGH DENSITY LIPOPROTEIN; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERCELLULAR ADHESION MOLECULE 1; INTERLEUKIN 1; LOW DENSITY LIPOPROTEIN; MONOCYTE CHEMOTACTIC PROTEIN 1; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR DELTA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; PIOGLITAZONE; PIRINIXIC ACID; PROSTAGLANDIN SYNTHASE; RETINOID X RECEPTOR; ROSIGLITAZONE; UNINDEXED DRUG; VASCULAR CELL ADHESION MOLECULE 1;

ADIPOCYTE; ATHEROSCLEROSIS; BLOOD PRESSURE REGULATION; CELL DIFFERENTIATION; GLUCOSE METABOLISM; HEART HYPERTROPHY; HEART MUSCLE ISCHEMIA; HUMAN; HYPERTENSION; LIPID METABOLISM; NONHUMAN; PATHOPHYSIOLOGY; PRIORITY JOURNAL; RECEPTOR BINDING; REPERFUSION INJURY; REVIEW; SIGNAL TRANSDUCTION; THROMBOSIS; TISSUE DISTRIBUTION; VASCULAR ENDOTHELIUM;

ANIMALS; CARDIOVASCULAR DISEASES; CARDIOVASCULAR SYSTEM; HEALTH; HUMANS; PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS; THIAZOLIDINEDIONES;

EID: 67349155584     PISSN: 01637258     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.pharmthera.2009.03.003     Document Type: Review

References (255)

1. Aasum E., Hafstad A.D., Severson D.L., and Larsen T.S. Age-dependent changes in metabolism, contractile function, and ischemic sensitivity in hearts from db/db mice. Diabetes 52 (2003) 434-441
2. Abate N. Obesity and cardiovascular disease. Pathogenetic role of the metabolic syndrome and therapeutic implications. J Diabetes Complications 14 (2000) 154-174
3. Achmad T.H., and Rao G.S. Chemotaxis of human blood monocytes toward endothelin-1 and the influence of calcium channel blockers. Biochem Biophys Res Commun 189 (1992) 994-1000
4. Adams M., Reginato M.J., Shao D., Lazar M.A., and Chatterjee V.K. Transcriptional activation by peroxisome proliferator-activated receptor gamma is inhibited by phosphorylation at a consensus mitogen-activated protein kinase site. J Biol Chem 272 (1997) 5128-5132
5. Aggeli I.K., Gaitanaki C., and Beis I. Involvement of JNKs and p38-MAPK/MSK1 pathways in H2O2-induced upregulation of heme oxygenase-1 mRNA in H9c2 cells. Cell Signal 18 (2006) 1801-1812
6. Akiyama T.E., Sakai S., Lambert G., Nicol C.J., Matsusue K., Pimprale S., et al. Conditional disruption of the peroxisome proliferator-activated receptor gamma gene in mice results in lowered expression of ABCA1, ABCG1, and apoE in macrophages and reduced cholesterol efflux. Mol Cell Biol 22 (2002) 2607-2619
7. Arakawa K., Ishihara T., Aoto M., Inamasu M., Kitamura K., and Saito A. An antidiabetic thiazolidinedione induces eccentric cardiac hypertrophy by cardiac volume overload in rats. Clin Exp Pharmacol Physiol 31 (2004) 8-13
8. Asakawa M., Takano H., Nagai T., Uozumi H., Hasegawa H., Kubota N., et al. Peroxisome proliferator-activated receptor gamma plays a critical role in inhibition of cardiac hypertrophy in vitro and in vivo. Circulation 105 (2002) 1240-1246
9. Babaev V.R., Yancey P.G., Ryzhov S.V., Kon V., Breyer M.D., Magnuson M.A., et al. Conditional knockout of macrophage PPARgamma increases atherosclerosis in C57BL/6 and low-density lipoprotein receptor-deficient mice. Arterioscler Thromb Vasc Biol 25 (2005) 1647-1653
10. Balakumar P., Rose M., Ganti S.S., Krishan P., and Singh M. PPAR dual agonists: Are they opening Pandora's Box?. Pharmacol Res 56 (2007) 91-98
11. Barger P.M., Brandt J.M., Leone T.C., Weinheimer C.J., and Kelly D.P. Deactivation of peroxisome proliferator-activated receptor-alpha during cardiac hypertrophic growth. J Clin Invest 105 (2000) 1723-1730
12. Barger P.M., and Kelly D.P. PPAR signaling in the control of cardiac energy metabolism. Trends Cardiovasc Med 10 (2000) 238-245
13. Barger P.M., Browning A.C., Garner A.N., and Kelly D.P. p38 mitogen-activated protein kinase activates peroxisome proliferator-activated receptor alpha: A potential role in the cardiac metabolic stress response. J Biol Chem 276 (2001) 44495-44501
14. Bensinger S.J., and Tontonoz P. Integration of metabolism and inflammation by lipid-activated nuclear receptors. Nature 454 (2008) 470-477
15. Berger J., Leibowitz M.D., Doebber T.W., Elbrecht A., Zhang B., Zhou G., et al. Novel peroxisome proliferator-activated receptor (PPAR) gamma and PPARdelta ligands produce distinct biological effects. J Biol Chem 274 (1999) 6718-6725
16. Berger J., and Moller D.E. The mechanisms of action of PPARs. Annu Rev Med 53 (2002) 409-435
17. Bishop S.P., and Altschuld R.A. Increased glycolytic metabolism in cardiac hypertrophy and congestive failure. Am J Physiol 218 (1970) 153-159
18. Blumberg B., and Evans R.M. Orphan nuclear receptors-New ligands and new possibilities. Genes Dev 12 (1998) 3149-3155
19. Bouhlel M.A., Derudas B., Rigamonti E., Dievart R., Brozek J., Haulon S., et al. PPARgamma activation primes human monocytes into alternative M2 macrophages with anti-inflammatory properties. Cell Metab 6 (2007) 137-143
20. Braissant O., Foufelle F., Scotto C., Dauca M., and Wahli W. Differential expression of peroxisome proliferator-activated receptors (PPARs): Tissue distribution of PPAR-alpha, -beta, and -gamma in the adult rat. Endocrinology 137 (1996) 354-366
21. Brandt J.M., Djouadi F., and Kelly D.P. Fatty acids activate transcription of the muscle carnitine palmitoyltransferase I gene in cardiac myocytes via the peroxisome proliferator-activated receptor alpha. J Biol Chem 273 (1998) 23786-23792
22. Brown M.S., and Goldstein J.L. Lipoprotein metabolism in the macrophage: Implications for cholesterol deposition in atherosclerosis. Annu Rev Biochem 52 (1983) 223-261
23. Brown M.S., and Goldstein J.L. Atherosclerosis. Scavenging for receptors. Nature 343 (1990) 508-509
24. Bruemmer D., Blaschke F., and Law R.E. New targets for PPARgamma in the vessel wall: Implications for restenosis. Int J Obes (Lond) 29 Suppl 1 (2005) S26-S30
25. Bulhak A.A., Sjoquist P.O., Xu C.B., Edvinsson L., and Pernow J. Protection against myocardial ischaemia/reperfusion injury by PPAR-alpha activation is related to production of nitric oxide and endothelin-1. Basic Res Cardiol 101 (2006) 244-252
26. Caglayan E., Stauber B., Collins A.R., Lyon C.J., Yin F., Liu J., et al. Differential roles of cardiomyocyte and macrophage peroxisome proliferator-activated receptor gamma in cardiac fibrosis. Diabetes 57 (2008) 2470-2479
27. Calnek D.S., Mazzella L., Roser S., Roman J., and Hart C.M. Peroxisome proliferator-activated receptor gamma ligands increase release of nitric oxide from endothelial cells. Arterioscler Thromb Vasc Biol 23 (2003) 52-57
28. Camp H.S., and Tafuri S.R. Regulation of peroxisome proliferator-activated receptor gamma activity by mitogen-activated protein kinase. J Biol Chem 272 (1997) 10811-10816
29. Carmona M.C., Louche K., Nibbelink M., Prunet B., Bross A., Desbazeille M., et al. Fenofibrate prevents Rosiglitazone-induced body weight gain in ob/ob mice. Int J Obes (Lond) 29 (2005) 864-871
30. Chaput E., Saladin R., Silvestre M., and Edgar A.D. Fenofibrate and rosiglitazone lower serum triglycerides with opposing effects on body weight. Biochem Biophys Res Commun 271 (2000) 445-450
31. Chen J.D., and Evans R.M. A transcriptional co-repressor that interacts with nuclear hormone receptors. Nature 377 (1995) 454-457
32. Cheng L., Ding G., Qin Q., Xiao Y., Woods D., Chen Y.E., et al. Peroxisome proliferator-activated receptor delta activates fatty acid oxidation in cultured neonatal and adult cardiomyocytes. Biochem Biophys Res Commun 313 (2004) 277-286
33. Cheng L., Ding G., Qin Q., Huang Y., Lewis W., He N., et al. Cardiomyocyte-restricted peroxisome proliferator-activated receptor-delta deletion perturbs myocardial fatty acid oxidation and leads to cardiomyopathy. Nat Med 10 (2004) 1245-1250
34. Chevalier S., and Roberts R.A. Perturbation of rodent hepatocyte growth control by nongenotoxic hepatocarcinogens: Mechanisms and lack of relevance for human health (review). Oncol Rep 5 (1998) 1319-1327
35. 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
36. Chinetti-Gbaguidi G., Rigamonti E., Helin L., Mutka A.L., Lepore M., Fruchart J.C., et al. Peroxisome proliferator-activated receptor alpha controls cellular cholesterol trafficking in macrophages. J Lipid Res 46 (2005) 2717-2725
37. Chinetti G., Griglio S., Antonucci M., Torra I.P., Delerive P., Majd Z., et al. Activation of proliferator-activated receptors alpha and gamma induces apoptosis of human monocyte-derived macrophages. J Biol Chem 273 (1998) 25573-25580
38. Chinetti G., Lestavel S., Bocher V., Remaley A.T., Neve B., Torra I.P., 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
39. Chira E.C., McMillen T.S., Wang S., Haw III A., O, Brien K.D., Wight T.N., et al. Tesaglitazar, a dual peroxisome proliferator-activated receptor alpha/gamma agonist, reduces atherosclerosis in female low density lipoprotein receptor deficient mice. Atherosclerosis 195 (2007) 100-109
40. Christe M.E., and Rodgers R.L. Altered glucose and fatty acid oxidation in hearts of the spontaneously hypertensive rat. J Mol Cell Cardiol 26 (1994) 1371-1375
41. Conlon D. Goodbye glitazars?. Br J Diabetes Vasc Dis 6 (2006) 135-137
42. Delerive P., Martin-Nizard F., Chinetti G., Trottein F., Fruchart J.C., 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 85 (1999) 394-402
43. Delerive P., De B.K., Besnard S., Vanden B.W., Peters J.M., Gonzalez F.J., et al. 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 274 (1999) 32048-32054
44. Devchand P.R., Keller H., Peters J.M., Vazquez M., Gonzalez F.J., and Wahli W. The PPARalpha-leukotriene B4 pathway to inflammation control. Nature 384 (1996) 39-43
45. Dewald O., Sharma S., Adrogue J., Salazar R., Duerr G.D., Crapo J.D., et al. Downregulation of peroxisome proliferator-activated receptor-alpha gene expression in a mouse model of ischemic cardiomyopathy is dependent on reactive oxygen species and prevents lipotoxicity. Circulation 112 (2005) 407-415
46. Diep Q.N., and Schiffrin E.L. Increased expression of peroxisome proliferator-activated receptor-alpha and -gamma in blood vessels of spontaneously hypertensive rats. Hypertension 38 (2001) 249-254
47. Diep Q.N., Amiri F., Touyz R.M., Cohn J.S., Endemann D., Neves M.F., et al. PPARalpha activator effects on Ang II-induced vascular oxidative stress and inflammation. Hypertension 40 (2002) 866-871
48. Diep Q.N., Benkirane K., Amiri F., Cohn J.S., Endemann D., and Schiffrin E.L. PPAR alpha activator fenofibrate inhibits myocardial inflammation and fibrosis in angiotensin II-infused rats. J Mol Cell Cardiol 36 (2004) 295-304
49. Diep Q.N., El M.M., Cohn J.S., Endemann D., Amiri F., Virdis A., et al. Structure, endothelial function, cell growth, and inflammation in blood vessels of angiotensin II-infused rats: role of peroxisome proliferator-activated receptor-gamma. Circulation 105 (2002) 2296-2302
50. Diep Q.N., Touyz R.M., and Schiffrin E.L. Docosahexaenoic acid, a peroxisome proliferator-activated receptor-alpha ligand, induces apoptosis in vascular smooth muscle cells by stimulation of p38 mitogen-activated protein kinase. Hypertension 36 (2000) 851-855
51. Ding N.Z., Ma X.H., Diao H.L., Xu L.B., and Yang Z.M. Differential expression of peroxisome proliferator-activated receptor delta at implantation sites and in decidual cells of rat uterus. Reproduction 125 (2003) 817-825
52. Djouadi F., Weinheimer C.J., Saffitz J.E., Pitchford C., Bastin J., Gonzalez F.J., et al. A gender-related defect in lipid metabolism and glucose homeostasis in peroxisome proliferator-activated receptor alpha-deficient mice. J Clin Invest 102 (1998) 1083-1091
53. Dormandy J.A., Charbonnel B., Eckland D.J., Erdmann E., Massi-Benedetti M., Moules I.K., et al. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): A randomised controlled trial. Lancet 366 (2005) 1279-1289
54. Dragomir E., Tircol M., Manduteanu I., Voinea M., and Simionescu M. Aspirin and PPAR-alpha activators inhibit monocyte chemoattractant protein-1 expression induced by high glucose concentration in human endothelial cells. Vascul Pharmacol 44 (2006) 440-449
55. Dreyer C., Krey G., Keller H., Givel F., Helftenbein G., and Wahli W. Control of the peroxisomal beta-oxidation pathway by a novel family of nuclear hormone receptors. Cell 68 (1992) 879-887
56. Duan S.Z., Ivashchenko C.Y., Russell M.W., Milstone D.S., and Mortensen R.M. Cardiomyocyte-specific knockout and agonist of peroxisome proliferator-activated receptor-gamma both induce cardiac hypertrophy in mice. Circ Res 97 (2005) 372-379
57. Duan S.Z., Ivashchenko C.Y., Whitesall S.E., D, Alecy L.G., Duquaine D.C., Brosius III F.C., et al. Hypotension, lipodystrophy, and insulin resistance in generalized PPARgamma-deficient mice rescued from embryonic lethality. J Clin Invest 117 (2007) 812-822
58. Duan S.Z., Usher M.G., and Mortensen R.M. Peroxisome proliferator-activated receptor-gamma-mediated effects in the vasculature. Circ Res 102 (2008) 283-294
59. Duhaney T.A., Cui L., Rude M.K., Lebrasseur N.K., Ngoy S., De Silva D.S., et al. Peroxisome proliferator-activated receptor alpha-independent actions of fenofibrate exacerbates left ventricular dilation and fibrosis in chronic pressure overload. Hypertension 49 (2007) 1084-1094
60. Edgley A.J., Thalen P.G., Dahllof B., Lanne B., Ljung B., and Oakes N.D. PPARgamma agonist induced cardiac enlargement is associated with reduced fatty acid and increased glucose utilization in myocardium of Wistar rats. Eur J Pharmacol 538 (2006) 195-206
61. Egan B.M., Greene E.L., and Goodfriend T.L. Nonesterified fatty acids in blood pressure control and cardiovascular complications. Curr Hypertens Rep 3 (2001) 107-116
62. Erdmann E., and Wilcox R.G. Weighing up the cardiovascular benefits of thiazolidinedione therapy: The impact of increased risk of heart failure. Eur Heart J 29 (2008) 12-20
63. Escher P., and Wahli W. Peroxisome proliferator-activated receptors: Insight into multiple cellular functions. Mutat Res 448 (2000) 121-138
64. Etgen G.J., Oldham B.A., Johnson W.T., Broderick C.L., Montrose C.R., Brozinick J.T., et al. A tailored therapy for the metabolic syndrome: The dual peroxisome proliferator-activated receptor-alpha/gamma agonist LY465608 ameliorates insulin resistance and diabetic hyperglycemia while improving cardiovascular risk factors in preclinical models. Diabetes 51 (2002) 1083-1087
65. Faggiotto A., Ross R., and Harker L. Studies of hypercholesterolemia in the nonhuman primate. I. Changes that lead to fatty streak formation. Arteriosclerosis 4 (1984) 323-340
66. Fajas L., Auboeuf D., Raspe E., Schoonjans K., Lefebvre A.M., Saladin R., et al. The organization, promoter analysis, and expression of the human PPARgamma gene. J Biol Chem 272 (1997) 18779-18789
67. Finck B.N., Lehman J.J., Leone T.C., Welch M.J., Bennett M.J., Kovacs A., et al. The cardiac phenotype induced by PPARalpha overexpression mimics that caused by diabetes mellitus. J Clin Invest 109 (2002) 121-130
68. Forman B.M., Chen J., and Evans R.M. Hypolipidemic drugs, polyunsaturated fatty acids, and eicosanoids are ligands for peroxisome proliferator-activated receptors alpha and delta. Proc Natl Acad Sci USA 94 (1997) 4312-4317
69. Forman B.M., Tontonoz P., Chen J., Brun R.P., Spiegelman B.M., and Evans R.M. 15-Deoxy-delta 12, 14-prostaglandin J2 is a ligand for the adipocyte determination factor PPAR gamma. Cell 83 (1995) 803-812
70. Francis G.S., and Young J.B. The looming polypharmacy crisis in the management of patients with heart failure. Potential solutions. Cardiol Clin 19 (2001) 541-545
71. Frangogiannis N.G., Smith C.W., and Entman M.L. The inflammatory response in myocardial infarction. Cardiovasc Res 53 (2002) 31-47
72. Frey N., and Olson E.N. Modulating cardiac hypertrophy by manipulating myocardial lipid metabolism?. Circulation 105 (2002) 1152-1154
73. Frey N., and Olson E.N. Cardiac hypertrophy: The good, the bad, and the ugly. Annu Rev Physiol 65 (2003) 45-79
74. Frick M.H., Elo O., Haapa K., Heinonen O.P., Heinsalmi P., Helo P., et al. Helsinki heart study: Primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia. Safety of treatment, changes in risk factors, and incidence of coronary heart disease. N Engl J Med 317 (1987) 1237-1245
75. Fruchart J.C. Novel peroxisome proliferator activated receptor-alpha agonists. Am J Cardiol 100 (2007) n41-n46
76. Gbaguidi F.G., Chinetti G., Milosavljevic D., Teissier E., Chapman J., Olivecrona G., et al. Peroxisome proliferator-activated receptor (PPAR) agonists decrease lipoprotein lipase secretion and glycated LDL uptake by human macrophages. FEBS Lett 512 (2002) 85-90
77. Geng D.F., Wu W., Jin D.M., Wang J.F., and Wu Y.M. Effect of peroxisome proliferator-activated receptor gamma ligand. Rosiglitazone on left ventricular remodeling in rats with myocardial infarction. Int J Cardiol 113 (2006) 86-91
78. Gervois P., Torra I.P., Chinetti G., Grotzinger T., Dubois G., Fruchart J.C., et al. A truncated human peroxisome proliferator-activated receptor alpha splice variant with dominant negative activity. Mol Endocrinol 13 (1999) 1535-1549
79. Giguere V. Orphan nuclear receptors: from gene to function. Endocr Rev 20 (1999) 689-725
80. Gilde A.J., and Van Bilsen M. Peroxisome proliferator-activated receptors (PPARS): Regulators of gene expression in heart and skeletal muscle. Acta Physiol Scand 178 (2003) 425-434
81. Gilde A.J., van der Lee K.A., Willemsen P.H., Chinetti G., van der Leij F.R., van d.V., et al. Peroxisome proliferator-activated receptor (PPAR) alpha and PPARbeta/delta, but not PPARgamma, modulate the expression of genes involved in cardiac lipid metabolism. Circ Res 92 (2003) 518-524
82. Goldstein J.L., Ho Y.K., Basu S.K., and Brown M.S. Binding site on macrophages that mediates uptake and degradation of acetylated low density lipoprotein, producing massive cholesterol deposition. Proc Natl Acad Sci USA 76 (1979) 333-337
83. Gonon A.T., Bulhak A., Labruto F., Sjoquist P.O., and Pernow J. Cardioprotection mediated by rosiglitazone, a peroxisome proliferator-activated receptor gamma ligand, in relation to nitric oxide. Basic Res Cardiol 102 (2007) 80-89
84. Gonzalez F.J., Peters J.M., and Cattley R.C. Mechanism of action of the nongenotoxic peroxisome proliferators: Role of the peroxisome proliferator-activator receptor alpha. J Natl Cancer Inst 90 (1998) 1702-1709
85. Gottlicher M., Widmark E., Li Q., and Gustafsson J.A. Fatty acids activate a chimera of the clofibric acid-activated receptor and the glucocorticoid receptor. Proc Natl Acad Sci USA 89 (1992) 4653-4657
86. Goya K., Sumitani S., Xu X., Kitamura T., Yamamoto H., Kurebayashi S., et al. Peroxisome proliferator-activated receptor alpha agonists increase nitric oxide synthase expression in vascular endothelial cells. Arterioscler Thromb Vasc Biol 24 (2004) 658-663
87. Gradman A.H., and Alfayoumi F. From left ventricular hypertrophy to congestive heart failure: management of hypertensive heart disease. Prog Cardiovasc Dis 48 (2006) 326-341
88. Graham T.L., Mookherjee C., Suckling K.E., Palmer C.N., and Patel L. The PPARdelta agonist GW0742X reduces atherosclerosis in LDLR(-/-) mice. Atherosclerosis 181 (2005) 29-37
89. Greene M.E., Blumberg B., McBride O.W., Yi H.F., Kronquist K., Kwan K., et al. Isolation of the human peroxisome proliferator activated receptor gamma cDNA: Expression in hematopoietic cells and chromosomal mapping. Gene Expr 4 (1995) 281-299
90. Grinsell J.W., Lardinois C.K., Swislocki A., Gonzalez R., Sare J.S., Michaels J.R., et al. Pioglitazone attenuates basal and postprandial insulin concentrations and blood pressure in the spontaneously hypertensive rat. Am J Hypertens 13 (2000) 370-375
91. Grundy S.M. Obesity, metabolic syndrome, and cardiovascular disease. J Clin Endocrinol Metab 89 (2004) 2595-2600
92. Guellich A., Damy T., Lecarpentier Y., Conti M., Claes V., Samuel J.L., et al. Role of oxidative stress in cardiac dysfunction of PPARalpha-/- mice. Am J Physiol Heart Circ Physiol 293 (2007) H93-H102
93. Gupta R.A., Tan J., Krause W.F., Geraci M.W., Willson T.M., Dey S.K., et al. Prostacyclin-mediated activation of peroxisome proliferator-activated receptor delta in colorectal cancer. Proc Natl Acad Sci USA 97 (2000) 13275-13280
94. Hamano T., Kobayashi K., Sakairi T., Hayashi M., and Mutai M. Peroxisome proliferator-activated receptor alpha (PPAR alpha) agonist, Wy 14,643, increased transcription of myosin light chain-2 in cardiomyocytes. J Toxicol Sci 26 (2001) 275-284
95. Han C., Demetris A.J., Michalopoulos G., Shelhamer J.H., and Wu T. 85-kDa cPLA(2) plays a critical role in PPAR-mediated gene transcription in human hepatoma cells. Am J Physiol Gastrointest Liver Physiol 282 (2002) G586-G597
96. Han J., Hajjar D.P., Tauras J.M., Feng J., Gotto Jr. A.M., and Nicholson A.C. Transforming growth factor-beta1 (TGF-beta1) and TGF-beta2 decrease expression of CD36, the type B scavenger receptor, through mitogen-activated protein kinase phosphorylation of peroxisome proliferator-activated receptor-gamma. J Biol Chem 275 (2000) 1241-1246
97. Haraguchi G., Kobayashi Y., Brown M.L., Tanaka A., Isobe M., Gianturco S.H., et al. PPAR(alpha) and PPAR(gamma) activators suppress the monocyte-macrophage apoB-48 receptor. J Lipid Res 44 (2003) 1224-1231
98. Harman F.S., Nicol C.J., Marin H.E., Ward J.M., Gonzalez F.J., and Peters J.M. Peroxisome proliferator-activated receptor-delta attenuates colon carcinogenesis. Nat Med 10 (2004) 481-483
99. Healey J.S., and Connolly S.J. Atrial fibrillation: Hypertension as a causative agent, risk factor for complications, and potential therapeutic target. Am J Cardiol 91 (2003) 9G-14G
100. Henderson B.C., Sen U., Reynolds C., Moshal K.S., Ovechkin A., Tyagi N., et al. Reversal of systemic hypertension-associated cardiac remodeling in chronic pressure overload myocardium by ciglitazone. Int J Biol Sci 3 (2007) 385-392
101. Horlein A.J., Naar A.M., Heinzel T., Torchia J., Gloss B., Kurokawa R., et al. Ligand-independent repression by the thyroid hormone receptor mediated by a nuclear receptor co-repressor. Nature 377 (1995) 397-404
102. Ichihara S., Obata K., Yamada Y., Nagata K., Noda A., Ichihara G., et al. Attenuation of cardiac dysfunction by a PPAR-alpha agonist is associated with down-regulation of redox-regulated transcription factors. J Mol Cell Cardiol 41 (2006) 318-329
103. Iglarz M., Touyz R.M., Viel E.C., Paradis P., Amiri F., Diep Q.N., et al. Peroxisome proliferator-activated receptor-alpha and receptor-gamma activators prevent cardiac fibrosis in mineralocorticoid-dependent hypertension. Hypertension 42 (2003) 737-743
104. IJpenberg A., Jeannin E., Wahli W., and 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 272 (1997) 20108-20117
105. Inoue I., Shino K., Noji S., Awata T., and Katayama S. Expression of peroxisome proliferator-activated receptor alpha (PPAR alpha) in primary cultures of human vascular endothelial cells. Biochem Biophys Res Commun 246 (1998) 370-374
106. 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 109 (2004) 904-910
107. Ishibashi M., Egashira K., Hiasa K., Inoue S., Ni W., Zhao Q., et al. Antiinflammatory and antiarteriosclerotic effects of pioglitazone. Hypertension 40 (2002) 687-693
108. Issemann I., and Green S. Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature 347 (1990) 645-650
109. Ito H., Nakano A., Kinoshita M., and Matsumori A. Pioglitazone, a peroxisome proliferator-activated receptor-gamma agonist, attenuates myocardial ischemia/reperfusion injury in a rat model. Lab Invest 83 (2003) 1715-1721
110. Jackson L., Wahli W., Michalik L., Watson S.A., Morris T., Anderton K., et al. Potential role for peroxisome proliferator activated receptor (PPAR) in preventing colon cancer. Gut 52 (2003) 1317-1322
111. Jamshidi Y., Montgomery H.E., Hense H.W., Myerson S.G., Torra I.P., Staels B., et al. Peroxisome proliferator-activated receptor alpha gene regulates left ventricular growth in response to exercise and hypertension. Circulation 105 (2002) 950-955
112. Jiang C., Ting A.T., and Seed B. PPAR-gamma agonists inhibit production of monocyte inflammatory cytokines. Nature 391 (1998) 82-86
113. Johnson T.E., Holloway M.K., Vogel R., Rutledge S.J., Perkins J.J., Rodan G.A., et al. Structural requirements and cell-type specificity for ligand activation of peroxisome proliferator-activated receptors. J Steroid Biochem Mol Biol 63 (1997) 1-8
114. Jones G.T., van Rij A.M., Solomon C., Thomson I.A., and Packer S.G. Endothelin-1 is increased overlying atherosclerotic plaques in human arteries. Atherosclerosis 124 (1996) 25-35
115. Juge-Aubry C.E., Hammar E., Siegrist-Kaiser C., Pernin A., Takeshita A., Chin W.W., et al. Regulation of the transcriptional activity of the peroxisome proliferator-activated receptor alpha by phosphorylation of a ligand-independent trans-activating domain. J Biol Chem 274 (1999) 10505-10510
116. Kang K., Reilly S.M., Karabacak V., Gangl M.R., Fitzgerald K., Hatano B., et al. Adipocyte-derived Th2 cytokines and myeloid PPARdelta regulate macrophage polarization and insulin sensitivity. Cell Metab 7 (2008) 485-495
117. Kannel W.B. Hazards, risks, and threats of heart disease from the early stages to symptomatic coronary heart disease and cardiac failure. Cardiovasc Drugs Ther 11 Suppl 1 (1997) 199-212
118. Kaplan J., Cook J.A., O, Connor M., and Zingarelli B. Peroxisome proliferator-activated receptor gamma is required for the inhibitory effect of ciglitazone but not 15-deoxy-Delta 12,14-prostaglandin J2 on the NFkappaB pathway in human endothelial cells. Shock 28 (2007) 722-726
119. Keech A., Simes R.J., Barter P., Best J., Scott R., Taskinen M.R., 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 366 (2005) 1849-1861
120. Kelly D.P., and Strauss A.W. Inherited cardiomyopathies. N Engl J Med 330 (1994) 913-919
121. Khandoudi N., Delerive P., Berrebi-Bertrand I., Buckingham R.E., Staels B., and Bril A. Rosiglitazone, a peroxisome proliferator-activated receptor-gamma, inhibits the Jun NH(2)-terminal kinase/activating protein 1 pathway and protects the heart from ischemia/reperfusion injury. Diabetes 51 (2002) 1507-1514
122. Kliewer S.A., Forman B.M., Blumberg B., Ong E.S., Borgmeyer U., Mangelsdorf D.J., et al. Differential expression and activation of a family of murine peroxisome proliferator-activated receptors. Proc Natl Acad Sci USA 91 (1994) 7355-7359
123. Kliewer S.A., Lenhard J.M., Willson T.M., Patel I., Morris D.C., and Lehmann J.M. A prostaglandin J2 metabolite binds peroxisome proliferator-activated receptor gamma and promotes adipocyte differentiation. Cell 83 (1995) 813-819
124. Kliewer S.A., Sundseth S.S., Jones S.A., Brown P.J., Wisely G.B., Koble C.S., et al. Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors alpha and gamma. Proc Natl Acad Sci USA 94 (1997) 4318-4323
125. Kliewer S.A., Umesono K., Noonan D.J., Heyman R.A., and Evans R.M. Convergence of 9-cis retinoic acid and peroxisome proliferator signalling pathways through heterodimer formation of their receptors. Nature 358 (1992) 771-774
126. Kliewer S.A., Xu H.E., Lambert M.H., and Willson T.M. Peroxisome proliferator-activated receptors: from genes to physiology. Recent Prog Horm Res 56 (2001) 239-263
127. Knopp R.H. Drug treatment of lipid disorders. N Engl J Med 341 (1999) 498-511
128. Kobori H., Ozawa Y., Suzaki Y., and Nishiyama A. Enhanced intrarenal angiotensinogen contributes to early renal injury in spontaneously hypertensive rats. J Am Soc Nephrol 16 (2005) 2073-2080
129. Kota B.P., Huang T.H., and Roufogalis B.D. An overview on biological mechanisms of PPARs. Pharmacol Res 51 (2005) 85-94
130. Kubota T., Koshizuka K., Williamson E.A., Asou H., Said J.W., Holden S., et al. Ligand for peroxisome proliferator-activated receptor gamma (troglitazone) has potent antitumor effect against human prostate cancer both in vitro and in vivo. Cancer Res 58 (1998) 3344-3352
131. Law R.E., Goetze S., Xi X.P., Jackson S., Kawano Y., Demer L., et al. Expression and function of PPARgamma in rat and human vascular smooth muscle cells. Circulation 101 (2000) 1311-1318
132. Law R.E., Meehan W.P., Xi X.P., Graf K., Wuthrich D.A., Coats W., et al. Troglitazone inhibits vascular smooth muscle cell growth and intimal hyperplasia. J Clin Invest 98 (1996) 1897-1905
133. Lee T.M., and Chou T.F. Troglitazone administration limits infarct size by reduced phosphorylation of canine myocardial connexin43 proteins. Am J Physiol Heart CircPhysiol 285 (2003) H1650-H1659
134. Lee C.H., Kang K., Mehl I.R., Nofsinger R., Alaynick W.A., Chong L.W., et al. Peroxisome proliferator-activated receptor delta promotes very low-density lipoprotein-derived fatty acid catabolism in the macrophage. Proc Natl Acad Sci USA 103 (2006) 2434-2439
135. Lee H., Shi W., Tontonoz P., Wang S., Subbanagounder G., Hedrick C.C., 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
136. Lehmann J.M., Lenhard J.M., Oliver B.B., Ringold G.M., and Kliewer S.A. Peroxisome proliferator-activated receptors alpha and gamma are activated by indomethacin and other non-steroidal anti-inflammatory drugs. J Biol Chem 272 (1997) 3406-3410
137. Lemberger T., Saladin R., Vazquez M., Assimacopoulos F., Staels B., Desvergne B., et al. Expression of the peroxisome proliferator-activated receptor alpha gene is stimulated by stress and follows a diurnal rhythm. J Biol Chem 271 (1996) 1764-1769
138. Li A.C., Binder C.J., Gutierrez A., Brown K.K., Plotkin C.R., Pattison J.W., et al. Differential inhibition of macrophage foam-cell formation and atherosclerosis in mice by PPARalpha, beta/delta, and gamma. J Clin Invest 114 (2004) 1564-1576
139. Li C., Browder W., and Kao R.L. Early activation of transcription factor NF-kappaB during ischemia in perfused rat heart. Am J Physiol 276 (1999) H543-H552
140. Li A.C., Brown K.K., Silvestre M.J., Willson T.M., Palinski W., and Glass C.K. Peroxisome proliferator-activated receptor gamma ligands inhibit development of atherosclerosis in LDL receptor-deficient mice. J Clin Invest 106 (2000) 523-531
141. Li C.B., Li X.X., Chen Y.G., Zhang C., Zhang M.X., Zhao X.Q., et al. Effects and mechanisms of PPARalpha activator fenofibrate on myocardial remodeling in hypertension. J Cell Mol Med (2008)
142. 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 581 (2007) 3311-3316
143. Liang F., Wang F., Zhang S., and Gardner D.G. Peroxisome proliferator activated receptor (PPAR)alpha agonists inhibit hypertrophy of neonatal rat cardiac myocytes. Endocrinology 144 (2003) 4187-4194
144. Libby P., Geng Y.J., Aikawa M., Schoenbeck U., Mach F., Clinton S.K., et al. Macrophages and atherosclerotic plaque stability. Curr Opin Lipidol 7 (1996) 330-335
145. Lim H., Gupta R.A., Ma W.G., Paria B.C., Moller D.E., Morrow J.D., et al. Cyclo-oxygenase-2-derived prostacyclin mediates embryo implantation in the mouse via PPARdelta. Genes Dev 13 (1999) 1561-1574
146. Lin J., Puigserver P., Donovan J., Tarr P., and Spiegelman B.M. Peroxisome proliferator-activated receptor gamma coactivator 1beta (PGC-1beta), a novel PGC-1-related transcription coactivator associated with host cell factor. J Biol Chem 277 (2002) 1645-1648
147. Lindberg M., and Astrup A. The role of glitazones in management of type 2 diabetes. A dream or a nightmare?. Obes Rev 8 (2007) 381-384
148. Liu H.R., Tao L., Gao E., Lopez B.L., Christopher T.A., Willette R.N., et al. Anti-apoptotic effects of rosiglitazone in hypercholesterolemic rabbits subjected to myocardial ischemia and reperfusion. Cardiovasc Res 62 (2004) 135-144
149. Lock E.A., Mitchell A.M., and Elcombe C.R. Biochemical mechanisms of induction of hepatic peroxisome proliferation. Annu Rev Pharmacol Toxicol 29 (1989) 145-163
150. Loichot C., Jesel L., Tesse A., Tabernero A., Schoonjans K., Roul G., et al. Deletion of peroxisome proliferator-activated receptor-alpha induces an alteration of cardiac functions. Am J Physiol Heart Circ Physiol 291
151. Luptak I., Balschi J.A., Xing Y., Leone T.C., Kelly D.P., and Tian R. Decreased contractile and metabolic reserve in peroxisome proliferator-activated receptor-alpha-null hearts can be rescued by increasing glucose transport and utilization. Circulation 112 (2005) 2339-2346
152. Lygate C.A., Hulbert K., Monfared M., Cole M.A., Clarke K., and Neubauer S. The PPARgamma-activator rosiglitazone does not alter remodeling but increases mortality in rats post-myocardial infarction. Cardiovasc Res 58 (2003) 632-637
153. Majai G., Sarang Z., Csomos K., Zahuczky G., and Fesus L. PPARgamma-dependent regulation of human macrophages in phagocytosis of apoptotic cells. Eur J Immunol 37 (2007) 1343-1354
154. Mangelsdorf D.J., and Evans R.M. The RXR heterodimers and orphan receptors. Cell 83 (1995) 841-850
155. Marx N., Mach F., Sauty A., Leung J.H., Sarafi M.N., Ransohoff R.M., et al. Peroxisome proliferator-activated receptor-gamma activators inhibit IFN-gamma-induced expression of the T cell-active CXC chemokines IP-10, Mig, and I-TAC in human endothelial cells. J Immunol 164 (2000) 6503-6508
156. Marx N., Sukhova G.K., Collins T., Libby P., and Plutzky J. PPARalpha activators inhibit cytokine-induced vascular cell adhesion molecule-1 expression in human endothelial cells. Circulation 99 (1999) 3125-3131
157. Marx N., Sukhova G., Murphy C., Libby P., and Plutzky J. Macrophages in human atheroma contain PPARgamma: Differentiation-dependent peroxisomal proliferator-activated receptor gamma(PPARgamma) expression and reduction of MMP-9 activity through PPARgamma activation in mononuclear phagocytes in vitro. Am J Pathol 153 (1998) 17-23
158. Mazzone T., Meyer P.M., Feinstein S.B., Davidson M.H., Kondos G.T., D, Agostino Sr. R.B., et al. Effect of pioglitazone compared with glimepiride on carotid intima-media thickness in type 2 diabetes: A randomized trial. JAMA 296 (2006) 2572-2581
159. McCarron R.M., Wang L., Stanimirovic D.B., and Spatz M. Endothelin induction of adhesion molecule expression on human brain microvascular endothelial cells. Neurosci Lett 156 (1993) 31-34
160. Michalik L., Auwerx J., Berger J.P., Chatterjee V.K., Glass C.K., Gonzalez F.J., et al. International Union of Pharmacology. LXI. Peroxisome proliferator-activated receptors. Pharmacol Rev 58 (2006) 726-741
161. Molavi B., Chen J., and Mehta J.L. Cardioprotective effects of rosiglitazone are associated with selective overexpression of type 2 angiotensin receptors and inhibition of p42/44 MAPK. Am J Physiol Heart Circ Physiol 291 (2006) H687-H693
162. Moller D.E. Potential role of TNF-alpha in the pathogenesis of insulin resistance and type 2 diabetes. Trends Endocrinol Metab 11 (2000) 212-217
163. Morgan E.E., Rennison J.H., Young M.E., McElfresh T.A., Kung T.A., Tserng K.Y., et al. Effects of chronic activation of peroxisome proliferator-activated receptor-alpha or high-fat feeding in a rat infarct model of heart failure. Am J Physiol Heart Circ Physiol 290 (2006) H1899-H1904
164. Mueller E., Sarraf P., Tontonoz P., Evans R.M., Martin K.J., Zhang M., et al. Terminal differentiation of human breast cancer through PPAR gamma. Mol Cell 1 (1998) 465-470
165. Nagy L., Tontonoz P., Alvarez J.G., Chen H., and Evans R.M. Oxidized LDL regulates macrophage gene expression through ligand activation of PPARgamma. Cell 93 (1998) 229-240
166. Newaz M., Blanton A., Fidelis P., and Oyekan A. NAD(P)H oxidase/nitric oxide interactions in peroxisome proliferator activated receptor (PPAR)alpha-mediated cardiovascular effects. Mutat Res 579 (2005) 163-171
167. Nissen S.E., and Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med 356 (2007) 2457-2471
168. Nissen S.E., Wolski K., and Topol E.J. Effect of muraglitazar on death and major adverse cardiovascular events in patients with type 2 diabetes mellitus. JAMA 294 (2005) 2581-2586
169. Nolte R.T., Wisely G.B., Westin S., Cobb J.E., Lambert M.H., Kurokawa R., et al. Ligand binding and co-activator assembly of the peroxisome proliferator-activated receptor-gamma. Nature 395 (1998) 137-143
170. Odegaard J.I., Ricardo-Gonzalez R.R., Goforth M.H., Morel C.R., Subramanian V., Mukundan L., et al. Macrophage-specific PPARgamma controls alternative activation and improves insulin resistance. Nature 447 (2007) 1116-1120
171. Odegaard J.I., Ricardo-Gonzalez R.R., Red E.A., Vats D., Morel C.R., Goforth M.H., et al. Alternative M2 activation of Kupffer cells by PPARdelta ameliorates obesity-induced insulin resistance. Cell Metab 7 (2008) 496-507
172. Ogata T., Miyauchi T., Sakai S., Irukayama-Tomobe Y., Goto K., and 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) 103 Suppl 48 (2002) 284S-288S
173. Okuno A., Tamemoto H., Tobe K., Ueki K., Mori Y., Iwamoto K., et al. Troglitazone increases the number of small adipocytes without the change of white adipose tissue mass in obese Zucker rats. J Clin Invest 101 (1998) 1354-1361
174. Oliver Jr. W.R., Shenk J.L., Snaith M.R., Russell C.S., Plunket K.D., Bodkin N.L., et al. A selective peroxisome proliferator-activated receptor delta agonist promotes reverse cholesterol transport. Proc Natl Acad Sci USA 98 (2001) 5306-5311
175. Onai Y., Suzuki J., Kakuta T., Maejima Y., Haraguchi G., Fukasawa H., et al. Inhibition of IkappaB phosphorylation in cardiomyocytes attenuates myocardial ischemia/reperfusion injury. Cardiovasc Res 63 (2004) 51-59
176. Otto M.E., Belohlavek M., Khandheria B., Gilman G., Svatikova A., and Somers V. Comparison of right and left ventricular function in obese and nonobese men. Am J Cardiol 93 (2004) 1569-1572
177. Panagia M., Gibbons G.F., Radda G.K., and Clarke K. PPAR-alpha activation required for decreased glucose uptake and increased susceptibility to injury during ischemia. Am J Physiol Heart Circ Physiol 288 (2005) H2677-H2683
178. Pasceri V., Wu H.D., Willerson J.T., and Yeh E.T. Modulation of vascular inflammation in vitro and in vivo by peroxisome proliferator-activated receptor-gamma activators. Circulation 101 (2000) 235-238
179. Pellieux C., Montessuit C., Papageorgiou I., and Lerch R. Inactivation of peroxisome proliferator-activated receptor isoforms alpha, beta/delta, and gamma mediate distinct facets of hypertrophic transformation of adult cardiac myocytes. Pflugers Arch 455 (2007) 443-454
180. Piper H.M., Meuter K., and Schafer C. Cellular mechanisms of ischemia-reperfusion injury. Ann Thorac Surg 75 (2003) S644-S648
181. Planavila A., Rodriguez-Calvo R., Jove M., Michalik L., Wahli W., Laguna J.C., et al. Peroxisome proliferator-activated receptor beta/delta activation inhibits hypertrophy in neonatal rat cardiomyocytes. Cardiovasc Res 65 (2005) 832-841
182. Poynter M.E., and Daynes R.A. Peroxisome proliferator-activated receptor alpha activation modulates cellular redox status, represses nuclear factor-kappaB signaling, and reduces inflammatory cytokine production in aging. J Biol Chem 273 (1998) 32833-32841
183. Puigserver P., Wu Z., Park C.W., Graves R., Wright M., and Spiegelman B.M. A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell 92 (1998) 829-839
184. Reddy J.K., and Krishnakantha T.P. Hepatic peroxisome proliferation: Induction by two novel compounds structurally unrelated to clofibrate. Science 190 (1975) 787-789
185. Ricote M., Huang J., Fajas L., Li A., Welch J., Najib J., et al. Expression of the peroxisome proliferator-activated receptor gamma (PPARgamma) in human atherosclerosis and regulation in macrophages by colony stimulating factors and oxidized low density lipoprotein. Proc Natl Acad Sci USA 95 (1998) 7614-7619
186. Ricote M., Huang J.T., Welch J.S., and Glass C.K. The peroxisome proliferator-activated receptor(PPARgamma) as a regulator of monocyte/macrophage function. J Leukoc Biol 66 (1999) 733-739
187. Ricote M., Li A.C., Willson T.M., Kelly C.J., and Glass C.K. The peroxisome proliferator-activated receptor-gamma is a negative regulator of macrophage activation. Nature 391 (1998) 79-82
188. Ross R. Atherosclerosis-An inflammatory disease. N Engl J Med 340 (1999) 115-126
189. Rubins H.B., Robins S.J., Collins D., Fye C.L., Anderson J.W., Elam M.B., et al. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. N Engl J Med 341 (1999) 410-418
190. Sack M.N., Rader T.A., Park S., Bastin J., McCune S.A., and Kelly D.P. Fatty acid oxidation enzyme gene expression is downregulated in the failing heart. Circulation 94 (1996) 2837-2842
191. Sambandam N., Morabito D., Wagg C., Finck B.N., Kelly D.P., and Lopaschuk G.D. Chronic activation of PPARalpha is detrimental to cardiac recovery after ischemia. Am J Physiol Heart Circ Physiol 290 (2006) H87-H95
192. Sato H., Ishihara S., Kawashima K., Moriyama N., Suetsugu H., Kazumori H., et al. Expression of peroxisome proliferator-activated receptor (PPAR)gamma in gastric cancer and inhibitory effects of PPARgamma agonists. Br J Cancer 83 (2000) 1394-1400
193. Satoh H., Tsukamoto K., Hashimoto Y., Hashimoto N., Togo M., Hara M., et al. Thiazolidinediones suppress endothelin-1 secretion from bovine vascular endothelial cells: A new possible role of PPARgamma on vascular endothelial function. Biochem Biophys Res Commun 254 (1999) 757-763
194. Scandinavian Simvastatin Survival Study. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: The Scandinavian Simvastatin Survival Study (4S). Lancet 344 (1994) 1383-1389
195. Schiffrin E.L. Peroxisome proliferator-activated receptors and cardiovascular remodeling. Am J Physiol Heart Circ Physiol 288 (2005) H1037-H1043
196. Schmidt A., Endo N., Rutledge S.J., Vogel R., Shinar D., and Rodan G.A. Identification of a new member of the steroid hormone receptor superfamily that is activated by a peroxisome proliferator and fatty acids. Mol Endocrinol 6 (1992) 1634-1641
197. Schoonjans K., Peinado-Onsurbe J., Lefebvre A.M., Heyman R.A., Briggs M., 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 15 (1996) 5336-5348
198. Schoonjans K., Staels B., and 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 37 (1996) 907-925
199. Schulman I.H., Zhou M.S., and Raij L. Interaction between nitric oxide and angiotensin II in the endothelium: Role in atherosclerosis and hypertension. J Hypertens Suppl 24 (2006) S45-S50
200. Schuster H., Fagerberg B., Edwards S., Halmos T., Lopatynski J., Stender S., et al. Tesaglitazar, a dual peroxisome proliferator-activated receptor alpha/gamma agonist, improves apolipoprotein levels in non-diabetic subjects with insulin resistance. Atherosclerosis 197 (2008) 355-362
201. Shalev A., Siegrist-Kaiser C.A., Yen P.M., Wahli W., Burger A.G., Chin W.W., et al. The peroxisome proliferator-activated receptor alpha is a phosphoprotein: regulation by insulin. Endocrinology 137 (1996) 4499-4502
202. Shepherd J., Cobbe S.M., Ford I., Isles C.G., Lorimer A.R., MacFarlane P.W., et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. N Engl J Med 333 (1995) 1301-1307
203. Sher T., Yi H.F., McBride O.W., and Gonzalez F.J. cDNA cloning, chromosomal mapping, and functional characterization of the human peroxisome proliferator activated receptor. Biochemistry 32 (1993) 5598-5604
204. Shimabukuro M., Higa S., Shinzato T., Nagamine F., Komiya I., and Takasu N. Cardioprotective effects of troglitazone in streptozotocin-induced diabetic rats. Metabolism 45 (1996) 1168-1173
205. Shimaya A., Kurosaki E., Shioduka K., Nakano R., Shibasaki M., and Shikama H. YM268 increases the glucose uptake, cell differentiation, and mRNA expression of glucose transporter in 3T3-L1 adipocytes. Horm Metab Res 30 (1998) 543-548
206. Shu H., Wong B., Zhou G., Li Y., Berger J., Woods J.W., 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 267 (2000) 345-349
207. Sidell R.J., Cole M.A., Draper N.J., Desrois M., Buckingham R.E., and Clarke K. Thiazolidinedione treatment normalizes insulin resistance and ischemic injury in the Zucker fatty rat heart. Diabetes 51 (2002) 1110-1117
208. Sivarajah A., McDonald M.C., and Thiemermann C. The cardioprotective effects of preconditioning with endotoxin, but not ischemia, are abolished by a peroxisome proliferator-activated receptor-gamma antagonist. J Pharmacol Exp Ther 313 (2005) 896-901
209. Smeets P.J., Planavila A., van d.V., and Van B.M. Peroxisome proliferator-activated receptors and inflammation: Take it to heart. Acta Physiol (Oxf) 191 (2007) 171-188
210. Smeets P.J., Teunissen B.E., Planavila A., de Vogel-van den Bosch, Willemsen P.H., van d.V., et al. Inflammatory pathways are activated during cardiomyocyte hypertrophy and attenuated by peroxisome proliferator-activated receptors PPARalpha and PPARdelta. J Biol Chem 283 (2008) 29109-29118
211. Smeets P.J., Teunissen B.E., Willemsen P.H., van Nieuwenhoven F.A., Brouns A.E., Janssen B.J., et al. Cardiac hypertrophy is enhanced in PPAR alpha-/- mice in response to chronic pressure overload. Cardiovasc Res 78 (2008) 79-89
212. Smiley L.M., Camp T.M., Lucchesi P.A., and Tyagi S.C. Peroxisome proliferator ameliorates endocardial endothelial and muscarinic dysfunction in spontaneously hypertensive rats. Antioxid Redox Signal 6 (2004) 367-374
213. Soutoglou E., Viollet B., Vaxillaire M., Yaniv M., Pontoglio M., and Talianidis I. Transcription factor-dependent regulation of CBP and P/CAF histone acetyltransferase activity. EMBO J 20 (2001) 1984-1992
214. Springer T.A. Traffic signals for lymphocyte recirculation and leukocyte emigration: The multistep paradigm. Cell 76 (1994) 301-314
215. Staels B., Koenig W., Habib A., Merval R., Lebret M., Torra I.P., et al. Activation of human aortic smooth-muscle cells is inhibited by PPARalpha but not by PPARgamma activators. Nature 393 (1998) 790-793
216. Snghedauw B. Molecular mechanisms of myocardial remodeling. Physiol Rev 79 (1999) 215-262
217. Sugawara A., Takeuchi K., Uruno A., Ikeda Y., Arima S., Kudo M., et al. Transcriptional suppression of type 1 angiotensin II receptor gene expression by peroxisome proliferator-activated receptor-gamma in vascular smooth muscle cells. Endocrinology 142 (2001) 3125-3134
218. Tabernero A., Schoonjans K., Jesel L., Carpusca I., Auwerx J., and Andriantsitohaina R. Activation of the peroxisome proliferator-activated receptor alpha protects against myocardial ischaemic injury and improves endothelial vasodilatation. BMC Pharmacol 2 (2002) 10
219. Taegtmeyer H. Energy metabolism of the heart: from basic concepts to clinical applications. Curr Probl Cardiol 19 (1994) 59-113
220. Takeyama D., Kagaya Y., Yamane Y., Shiba N., Chida M., Takahashi T., et al. Effects of chronic right ventricular pressure overload on myocardial glucose and free fatty acid metabolism in the conscious rat. Cardiovasc Res 29 (1995) 763-767
221. Tan N.S., Shaw N.S., Vinckenbosch N., Liu P., Yasmin R., Desvergne B., et al. Selective cooperation between fatty acid binding proteins and peroxisome proliferator-activated receptors in regulating transcription. Mol Cell Biol 22 (2002) 5114-5127
222. Teissier E., Nohara A., Chinetti G., Paumelle R., Cariou B., Fruchart J.C., et al. Peroxisome proliferator-activated receptor alpha induces NADPH oxidase activity in macrophages, leading to the generation of LDL with PPAR-alpha activation properties. Circ Res 95 (2004) 1174-1182
223. Tenkanen L., Manttari 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
224. Tian Q., Grzemski F.A., Panagiotopoulos S., and Ahokas J.T. Peroxisome proliferator-activated receptor alpha agonist, clofibrate, has profound influence on myocardial fatty acid composition. Chem Biol Interact 160 (2006) 241-251
225. Todorov V.T., Desch M., Schmitt-Nilson N., Todorova A., and Kurtz A. Peroxisome proliferator-activated receptor-gamma is involved in the control of renin gene expression. Hypertension 50 (2007) 939-944
226. Tordjman K., Bernal-Mizrachi C., Zemany L., Weng S., Feng C., Zhang F., et al. PPARalpha deficiency reduces insulin resistance and atherosclerosis in apoE-null mice. J Clin Invest 107 (2001) 1025-1034
227. Tordjman K.M., Semenkovich C.F., Coleman T., Yudovich R., Bak S., Osher E., et al. Absence of peroxisome proliferator-activated receptor-alpha abolishes hypertension and attenuates atherosclerosis in the Tsukuba hypertensive mouse. Hypertension 50 (2007) 945-951
228. Vamecq J., and Draye J.P. Pathophysiology of peroxisomal beta-oxidation. Essays Biochem 24 (1989) 115-225
229. van der Lee K.A., Vork M.M., De Vries J.E., Willemsen P.H., Glatz J.F., Reneman R.S., et al. Long-chain fatty acid-induced changes in gene expression in neonatal cardiac myocytes. J Lipid Res 41 (2000) 41-47
230. van der Lee K.A., Willemsen P.H., van d.V., and Van B.M. Effects of fatty acids on uncoupling protein-2 expression in the rat heart. FASEB J 14 (2000) 495-502
231. van der Wal A.C., Das P.K., Tigges A.J., and Becker A.E. Adhesion molecules on the endothelium and mononuclear cells in human atherosclerotic lesions. Am J Pathol 141 (1992) 1427-1433
232. Verges B. Clinical interest of PPARs ligands. Diabetes Metab 30 (2004) 7-12
233. Verma S., Bhanot S., Arikawa E., Yao L., and McNeill J.H. Direct vasodepressor effects of pioglitazone in spontaneously hypertensive rats. Pharmacology 56 (1998) 7-16
234. Verreth W., Ganame J., Mertens A., Bernar H., Herregods M.C., and Holvoet P. Peroxisome proliferator-activated receptor-alpha,gamma-agonist improves insulin sensitivity and prevents loss of left ventricular function in obese dyslipidemic mice. Arterioscler Thromb Vasc Biol 26 (2006) 922-928
235. Vosper H., Khoudoli G.A., Graham T.L., and Palmer C.N. Peroxisome proliferator-activated receptor agonists, hyperlipidaemia, and atherosclerosis. Pharmacol Ther 95 (2002) 47-62
236. Walker A.B., Chattington P.D., Buckingham R.E., and Williams G. The thiazolidinedione rosiglitazone (BRL-49653) lowers blood pressure and protects against impairment of endothelial function in Zucker fatty rats. Diabetes 48 (1999) 1448-1453
237. Wayman N.S., Ellis B.L., and Thiemermann C. Ligands of the peroxisome proliferator-activated receptor-PPAR-a reduce myocardial infarct size. Med Sci Monit 8 (2002) BR243-BR247
238. Wayman N.S., Hattori Y., McDonald M.C., Mota-Filipe H., Cuzzocrea S., Pisano B., et al. Ligands of the peroxisome proliferator-activated receptors (PPAR-gamma and PPAR-alpha) reduce myocardial infarct size. FASEB J 16 (2002) 1027-1040
239. Weatherford E.T., Itani H., Keen H.L., and Sigmund C.D. Is peroxisome proliferator-activated receptor-gamma a new "pal" of renin?. Hypertension 50 (2007) 844-846
240. Werman A., Hollenberg A., Solanes G., Bjorbaek C., Vidal-Puig A.J., and Flier J.S. Ligand-independent activation domain in the N terminus of peroxisome proliferator-activated receptor gamma (PPARgamma). Differential activity of PPARgamma1 and -2 isoforms and influence of insulin. J Biol Chem 272 (1997) 20230-20235
241. Wu L., Wang R., De C.J., and Wilson T.W. Beneficial and deleterious effects of rosiglitazone on hypertension development in spontaneously hypertensive rats. Am J Hypertens 17 (2004) 749-756
242. Wynne A.M., Mocanu M.M., and Yellon D.M. Pioglitazone mimics preconditioning in the isolated perfused rat heart: A role for the prosurvival kinases PI3K and P42/44MAPK. J Cardiovasc Pharmacol 46 (2005) 817-822
243. Xu L., Glass C.K., and Rosenfeld M.G. Coactivator and corepressor complexes in nuclear receptor function. Curr Opin Genet Dev 9 (1999) 140-147
244. Xu Y., Lu L., Greyson C., Lee J., Gen M., Kinugawa K., et al. Deleterious effects of acute treatment with a peroxisome proliferator-activated receptor-gamma activator in myocardial ischemia and reperfusion in pigs. Diabetes 52 (2003) 1187-1194
245. Yagil C., and Yagil Y. Peroxisome proliferator-activated receptor alpha: Friend or foe?. Hypertension 50 (2007) 847-850
246. Yamamoto K., Ohki R., Lee R.T., Ikeda U., and Shimada K. Peroxisome proliferator-activated receptor gamma activators inhibit cardiac hypertrophy in cardiac myocytes. Circulation 104 (2001) 1670-1675
247. Yeh C.H., Chen T.P., Lee C.H., Wu Y.C., Lin Y.M., and Lin P.J. Cardiomyocytic apoptosis following global cardiac ischemia and reperfusion can be attenuated by peroxisome proliferator-activated receptor alpha but not gamma activators. Shock 26 (2006) 262-270
248. Young M.E., Laws F.A., Goodwin G.W., and Taegtmeyer H. Reactivation of peroxisome proliferator-activated receptor alpha is associated with contractile dysfunction in hypertrophied rat heart. J Biol Chem 276 (2001) 44390-44395
249. Yue T.L., Bao W., Jucker B.M., Gu J.L., Romanic A.M., Brown P.J., et al. Activation of peroxisome proliferator-activated receptor-alpha protects the heart from ischemia/reperfusion injury. Circulation 108 (2003) 2393-2399
250. Yue Tl T.L., Chen J., Bao W., Narayanan P.K., Bril A., Jiang W., et al. In vivo myocardial protection from ischemia/reperfusion injury by the peroxisome proliferator-activated receptor-gamma agonist rosiglitazone. Circulation 104 (2001) 2588-2594
251. Zahradka P. Cardiovascular actions of the peroxisome proliferator-activated receptor-alpha (PPARalpha) agonist Wy14,643. Cardiovasc Drug Rev 25 (2007) 99-122
252. Zhang L., and Chawla A. Role of PPARgamma in macrophage biology and atherosclerosis. Trends Endocrinol Metab 15 (2004) 500-505
253. Zhu P., Lu L., Xu Y., and Schwartz G.G. Troglitazone improves recovery of left ventricular function after regional ischemia in pigs. Circulation 101 (2000) 1165-1171
254. Zhu Y., Qi C., Jain S., Rao M.S., and Reddy J.K. Isolation and characterization of PBP, a protein that interacts with peroxisome proliferator-activated receptor. J Biol Chem 272 (1997) 25500-25506
255. Zingarelli B., Hake P.W., Mangeshkar P., O, Connor M., Burroughs T.J., Piraino G., et al. Diverse cardioprotective signaling mechanisms of peroxisome proliferator-activated receptor-gamma ligands, 15-deoxy-Delta12,14-prostaglandin J2 and ciglitazone, in reperfusion injury: role of nuclear factor-kappaB, heat shock factor 1, and Akt. Shock 28 (2007) 554-563