The PPAR genes, cardiovascular disease and the emergence of PPAR pharmacogenetics

Bibliography

• ISSEMANN I, GREEN S: Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature (1990) 347:645–650.
   PubMed Web of Science ®Google Scholar
• •Original description of the cloning of PPAR.
   Google Scholar
• DREYER C, KREY G, KELLER H, GIVEL F, HELFTENBEIN G, WAHLI W: Control of the peroxisomal beta-oxidation pathway by a novel family of nuclear hormone receptors. Cell (1992) 68:879–887.
   PubMed Web of Science ®Google Scholar
• BRAISSANT O, FOUFELLE F, SCOTTO C, DAUCA M, WAHLI W: Differential expression of peroxisome proliferator-activated receptors (PPARs): tissue distribution of PPAR-alpha, -beta, and -gamma in the adult rat. Endocrinology (1996) 137:354–366.
   PubMed Web of Science ®Google Scholar
• CHEW CH, SAMIAN MR, NAJIMUDIN N, TENGKU-MUHAMMAD TS: Molecular characterisation of six alternatively spliced variants and a novel promoter in human peroxisome proliferator-activated receptor alpha. Biochem. Biophys. Res. Commun. (2003) 305:235–243.
   PubMed Web of Science ®Google Scholar
• FAJAS L, AUBOEUF D, RASPE E et al.: The organization, promoter analysis, and expression of the human PPARgamma gene. Biol. Chem. (1997) 272:18779–18789.
   Web of Science ®Google Scholar
• FREDENRICH A. GRIMALDI Pk PPAR delta: an uncompletely known nuclear receptor. Diabetes Metab. (2005) 31:23–27.
   PubMed Web of Science ®Google Scholar
• MEIRHAEGHE A, FAJAS L, GOUILLEUX F et al.: A functional polymorphism in a STAT5B site of the human PPAR gamma 3 gene promoter affects height and lipid metabolism in a French population. Arterthscler. Thromb. Vasc. Biol. (2003) 23:289–294.
   PubMed Web of Science ®Google Scholar
• BERKENSTAM A, GUSTAFSSON JA: Nuclear receptors and their relevance to diseases related to lipid metabolism. Curr. Opin. PharmacoL (2005) 5:171–176.
   PubMed Web of Science ®Google Scholar
• ••An excellent overview of the nuclearhormone receptor family and discussion of high-affinity receptors, low-affinity receptors and non-receptor members.
   Google Scholar
• BENOIT G, MALEWICZ M, PERLMANN T: Digging deep into the pockets of orphan nuclear receptors: insights from structural studies. Trends Cell Biol. (2004) 14:369–376.
   PubMed Web of Science ®Google Scholar
• NOLTE RT, WISELY GB, WESTIN S et al.: Ligand binding and co-activator assembly of the peroxisome proliferator-activated receptor-gamma. Nature (1998) 395:137–143.
   PubMed Web of Science ®Google Scholar
• ZHU Y, KAN L, QI C et al.: Isolation and characterization of peroxisome proliferator-activated receptor (PPAR) interacting protein (PRIP) as a coactivator for PPAR. Biol. Chem. (2000) 275:13510–13516.
   Web of Science ®Google Scholar
• LEE K: Transactivation of peroxisome proliferator-activated receptor alpha by green tea extracts. J. Vet. Sci. (2004) 5:325–330.
   PubMedGoogle Scholar
• KLIEWER SA, UMESONO K, NOONAN DJ, HEYMAN RA, EVANS RM: Convergence of 9-cis retinoic acid and peroxisome proliferator signalling pathways through heterodimer formation of their receptors. Nature (1992) 358:771–774.
   PubMed Web of Science ®Google Scholar
• QI C, ZHU Y, REDDY JK: Peroxisome proliferator-activated receptors, coactivators, and downstream targets. Cell Biochem. Biophys. (2000) 32(Spring):187-204. An excellent review of tissue and species response to PPAR activation, with a discussion of competition for RXR, co-activators and co-repressors.
   Google Scholar
• SPIEGELMAN BM, PUIGSERVER P, WI] Z: Regulation of adipogenesis and energy balance by PPARgamma and PGC-1. Int. J. Obes. Relat. Metab. Disord. (2000) 24( Suppl. 4):58–10. An excellent review of the PGC-1 regulatory pathway in brown adipose and skeletal muscle.
   Google Scholar
• YU C, MARKAN K, TEMPLE KA, DEPLEWSKI D, BRADY MJ, COHEN RN: The nuclear receptor corepressors NCoR and SMRT decrease peroxisome proliferator-activated receptor gamma transcriptional activity and repress 3T3-L1 adipogenesis. j Biol. Chem. (2005) 280:13600–13605.
   PubMed Web of Science ®Google Scholar
• KROGSDAM AM, NIELSEN CA, NEVE S et al.: Nuclear receptor corepressor-dependent repression of peroxisome-proliferator-activated receptor delta-mediated transactivation. Biochem. J. (2002) 363:157–165.
   PubMed Web of Science ®Google Scholar
• PICARD F, KURTEV M, CHUNG N et al.: Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-gamma. Nature (2004) 429:771–776.
   PubMed Web of Science ®Google Scholar
• WESTIN S, KUROKAWA R, NOLTE RT et al.: Interactions controlling the assembly of nuclear-receptor heterodimers and co-activators. Nature (1998) 395:199–202.
   PubMed Web of Science ®Google Scholar
• LEHMAN JJ, BARGER PM, KOVACS A, SAFFITZ JE, MEDEIROS DM, KELLY DP: Peroxisome proliferator-activated receptor gamma coactivator-1 promotes cardiac mitochondrial biogenesis. Clin. Invest. (2000) 106:847–856.
   Google Scholar
• HUSS JM, KELLY DP: Nuclear receptorsignaling and cardiac energetics. Circ. Res. (2004) 95:568-578. An excellent review of PPARs and PGC-1 regulation of myocardial energy metabolism in the diseased heart.
   Google Scholar
• INOUE I, SHINO K, NOJI S, AWATA T, KATAYAMA S: Expression of peroxisome proliferator-activated receptor alpha (PPAR alpha) in primary cultures of human vascular endothelial cells. Biochem. Biophys. Res. Commun. (1998) 246:370–374.
   PubMed Web of Science ®Google Scholar
• STAELS B, KOENIG W, HABIB A et al.: Activation of human aortic smooth-muscle cells is inhibited by PPARalpha but not by PPARgamma activators. Nature (1998) 393:790–793.
   PubMed Web of Science ®Google Scholar
• JONES DC, DING X, DAYNES RA: Nuclear receptor peroxisome proliferator-activated receptor alpha (PPARalpha) is expressed in resting murine lymphocytes. The PPARalpha in T and B lymphocytes is both transactivation and transrepression competent. j Biol. Chem. (2002) 277:6838–6845.
   Google Scholar
• BARGER PM, BRANDT JM, LEONE TC, WEINHEIMER CJ, KELLY DP: Deactivation of peroxisome proliferator-activated receptor-alpha during cardiac hypertrophic growth. J. Clin. Invest. (2000) 105:1723–1730.
   PubMed Web of Science ®Google Scholar
• DJOUADI F, WEINHEIMER CJ, SAFFITZ JE et al.: A gender-related defect in lipid metabolism and glucose homeostasis in peroxisome proliferator-activated receptor alpha- deficient mice. J. Clin. Invest. (1998) 102:1083–1091.
   PubMed Web of Science ®Google Scholar
• FINCK BN, HAN X, COURTOIS M et al.: A critical role for PPARalpha-mediated lipotoxicity in the pathogenesis of diabetic cardiomyopathy: modulation by dietary fat content. Proc. Natl Acad. Sci.USA (2003) 100:1226–1231.
   PubMed Web of Science ®Google Scholar
• GUERRE-MILLO M, ROUAULT C, POULAIN P et al.: PPAR-alpha-null mice are protected from high-fat diet-induced insulin resistance. Diabetes (2001) 50:2809–2814.
   PubMed Web of Science ®Google Scholar
• HUSS JM, LEVY FH, KELLY DP: Hypoxia inhibits the peroxisome proliferator-activated receptor alpha/ retinoid X receptor gene regulatory pathway in cardiac myocytes: a mechanism for 02-dependent modulation of mitochondrial fatty acid oxidation. J. Biol. Chem. (2001) 276:27605–27612.
   PubMed Web of Science ®Google Scholar
• HUSS JM, KELLY DP: Mitochondrial energy metabolism in heart failure: a question of balance./ Clin. Invest. (2005) 115:547-555. An excellent review of the molecular regulatiion of mitochondrial energetic and metabolic abnormalities that occur in heart failure.
   Google Scholar
• LEMBERGER T, DESVERGNE B, WAHLI W: Peroxisome proliferator-activated receptors: a nuclear receptor signaling pathway in lipid physiology. Ann. Rev. Cell Dev. Biol. (1996) 12:335–363.
   PubMed Web of Science ®Google Scholar
• LEMBERGER T, SALADIN R, VAZQUEZ M et al.: Expression of the peroxisome proliferator-activated receptor alpha gene is stimulated by stress and follows a diurnal rhythm. J. Biol. Chem. (1996) 271:1764–1769.
   PubMed Web of Science ®Google Scholar
• LEONE TC, WEINHEIMER CJ, KELLY DP: A critical role for the peroxisome proliferator-activated receptor alpha (PPARalpha) in the cellular fasting response: the PPARalpha-null mouse as a model of fatty acid oxidation disorders. Proc. Natl Acad. Sci. USA (1999) 96:7473–7478.
   PubMed Web of Science ®Google Scholar
• CRESCI S, WRIGHT LD, SPRATT JA, BRIGGS FN, KELLY DP: Activation of a novel metabolic gene regulatory pathway by chronic stimulation of skeletal muscle. Am. J. PhysioL (1996) 270:C1413–C1420.
   Google Scholar
• IMAI T, TAKAKUWA R, MARCHAND S et al.: Peroxisome proliferator-activated receptor gamma is required in mature white and brown adipocytes for their survival in the mouse. Proc. Natl Acad. Sci. USA (2004) 101:4543–4547.
   PubMed Web of Science ®Google Scholar
• ROSEN ED, SARRAF P, TROY AE et al.: PPAR gamma is required for the differentiation of adipose tissue in vivo and in vitro. Mol Cell (1999) 4:611–617.
   PubMed Web of Science ®Google Scholar
• SPIEGELMAN BM: Peroxisome proliferator-activated receptor gamma: a key regulator of adipogenesis and systemic insulin sensitivity. Eur. J. Med. Res. (1997) 2:457-464. An excellent review of the role of PPAR in adipogenesis.
   Google Scholar
• MILES PD, BARAK Y, HEW, EVANS RM, OLEFSKY JM: Improved insulin-sensitivity in mice heterozygous for PPAR-gamma deficiency. J. Clin. Invest. (2000) 105:287–292.
   PubMed Web of Science ®Google Scholar
• AHIMA RS, FLIER JS: Adipose tissue as an endocrine organ. Trends Endocrinol Metab. (2000) 11:327–332.
   PubMed Web of Science ®Google Scholar
• LI AC, BINDER CJ, GUTIERREZ A et al.: Differential inhibition of macrophage foam-cell formation and atherosclerosis in mice by PPARalpha, beta/delta, and gamma. J. Clin. Invest. (2004) 114:1564–1576.
   PubMed Web of Science ®Google Scholar
• AMRI EZ, BONINO F, AILHAUD G, ABUMRAD NA, GRIMALDI PA: Cloning of a protein that mediates transcriptional effects of fatty acids in preadipocytes. Homology to peroxisome proliferator-activated receptors. J. Biol. Chem. (1995) 270:2367–2371.
   Google Scholar
• LEMBERGER T, BRAISSANT O, JUGE-AUBRY C et al.: PPAR tissue distribution and interactions with other hormone-signaling pathways. Ann. NY Acad. Sci. (1996) 804:231–251.
   PubMed Web of Science ®Google Scholar
• PETERS JM, LEE SS, LI Wet al.: Growth,adipose, brain, and skin alterations resulting from targeted disruption of the mouse peroxisome proliferator-activated receptor beta(delta). MoL Cell. Biol. (2000) 20:5119–5128.
   Google Scholar
• MATSUSUE K, PETERS JM, GONZALEZ FJ: PPARbeta/delta potentiates PPARgamma-stimulated adipocyte differentiation. FASEB J. (2004) 18:1477–1479.
   PubMed Web of Science ®Google Scholar
• TANAKA T, YAMAMOTO J, IWASAKI S et al.: Activation of peroxisome proliferator-activated receptor delta induces fatty acid beta-oxidation in skeletal muscle and attenuates metabolic syndrome. Proc. NatL Acad. Sci. USA (2003) 100:15924–15929.
   PubMed Web of Science ®Google Scholar
• CHENG L, DING G, QIN Q et ed.: Cardiomyocyte-restricted peroxisome proliferator-activated receptor-delta deletion perturbs myocardial fatty acid oxidation and leads to cardiomyopathy. Nat. Med. (2004) 10:1245–1250.
   Google Scholar
• PLANAVILA A, LAGUNA JC, VAZQUEZ-CARRERA M: Nuclear factor-kappaB activation leads to down-regulation of fatty acid oxidation during cardiac hypertrophy. J. Biol. Chem. (2005) 280:17464–17471.
   PubMed Web of Science ®Google Scholar
• PLANAVILA A, RODRIGUEZ-CALVO R, JOVE M et al.: Peroxisome proliferator-activated receptor beta/delta activation inhibits hypertrophy in neonatal rat cardiomyocytes. Cardiovasc. Res. (2005) 65:832–841.
   PubMed Web of Science ®Google Scholar
• DEWALD O, SHARMA S, ADROGUE J 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 (2005) 112:407–415.
   PubMed Web of Science ®Google Scholar
• SACK MN, RADER TA, PARKS, BASTIN J, MCCUNE SA, KELLY DP: Fatty acid oxidation enzyme gene expression is downregulated in the failing heart. Circulation (1996) 94:2837–2842.
   PubMed Web of Science ®Google Scholar
• FINCK BN, KELLY DP: Peroxisome proliferator-activated receptor alpha (PPARalpha) signaling in the gene regulatory control of energy metabolism in the normal and diseased heart. J. MoL Cell. CardioL (2002) 34:1249-1257. An excellent review of PPAR regulation of myocardial energy metabolism in the normal, hypertrophied, diabetic and hypoxic heart.
   Google Scholar
• SACK MN, DISCH DL, ROCKMAN HA, KELLY DP: A role for Sp and nuclear receptor transcription factors in a cardiac hypertrophic growth program. Proc. NatL Acad. Sci. USA (1997) 94:6438–6443.
   PubMed Web of Science ®Google Scholar
• RAZEGHI P, YOUNG ME, ALCORN JL, MORAVEC CS, FRAZIER OH, TAEGTMEYER H: Metabolic gene expression in fetal and failing human heart. Circulation (2001) 104:2923–2931.
   PubMed Web of Science ®Google Scholar
• FINCK BN, BERNAL-MIZRACHI C, HAN DH et al.: A potential link between muscle peroxisome proliferator-activated receptor-alpha signaling and obesity-related diabetes. Cell Metab. (2005) 1:133–144.
   PubMed Web of Science ®Google Scholar
• FINCK BN, LEHMAN JJ, LEONE TC et al.: The cardiac phenotype induced by PPARalpha overexpression mimics that caused by diabetes mellitus. J. Clin. Invest. (2002) 109:121–130.
   PubMed Web of Science ®Google Scholar
• KOSKINEN P, MANTTARI M, MANNINEN V, HUTTUNEN JK, HEINONEN OP, FRICK MH: Coronary heart disease incidence in NIDDM patients in the Helsinki Heart Study. Diabetes Care (1992) 15:820–825.
   PubMed Web of Science ®Google Scholar
• PANAGIA M, GIBBONS GF, RADDA GK, CLARKE K: PPARIalphal activation required for decreased glucose uptake and increased susceptibility to injury during ischemia. Am. J. PhysioL Heart Circ. PhysioL (2005) 288(6):H2677–H2683.
   Web of Science ®Google Scholar
• LYGATE CA, HULBERT K, MONFARED M, COLE MA, CLARKE K, NEUBAUER S: The PPARgamma-activator rosiglitazone does not alter remodeling but increases mortality in rats post-myocardial infarction. Cardiovasc. Res. (2003) 58:632–637.
   PubMed Web of Science ®Google Scholar
• YUE TL, BAO W, GU JL et al.: Rosiglitazone treatment in Zucker diabetic Fatty rats is associated with ameliorated cardiac insulin resistance and protection from ischemia/reperfusion-induced myocardial injury. Diabetes (2005) 54:554–562.
   PubMed Web of Science ®Google Scholar
• LIU HR, TAO L, GAO E et al.: Anti-apoptotic effects of rosiglitazone in hypercholesterolemic rabbits subjected to myocardial ischemia and reperfusion. Cardiovasc. Res. (2004) 62:135–144.
   PubMed Web of Science ®Google Scholar
• FORMAN BM, CHEN J, EVANS RM: Hypolipidemic drugs, polyunsaturated fatty acids, and eicosanoids are ligands for peroxisome proliferator-activated receptors alpha and delta. Proc. NatL Acad. Sci. USA (1997) 94:4312–4317.
   PubMed Web of Science ®Google Scholar
• KLIEWER SA, SUNDSETH SS, JONES SA 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 (1997) 94:4318–4323.
   PubMed Web of Science ®Google Scholar
• FRICK MH, ELO O, HAAPA K 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. (1987) 317:1237–1245.
   Google Scholar
• MANNINEN V, TENKANEN L, KOSKINEN P et al.: Joint effects of serum triglyceride and LDL cholesterol and HDL cholesterol concentrations on coronary heart disease risk in the Helsinki Heart Study. Implications for treatment. Circulation (1992) 85:37–45.
   PubMed Web of Science ®Google Scholar
• ROBINS SJ, COLLINS D, WITTES JT et al.: Relation of gemfibrozil treatment and lipid levels with major coronary events: VA-HIT: a randomized controlled trial. JANIA (2001) 285:1585–1591.
   PubMed Web of Science ®Google Scholar
• RUBINS HB, ROBINS SJ, COLLINS D et al.: Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. N EngL .1. Med. (1999) 341:410–418.
   Google Scholar
• BLOOMFIELD RH, DAVENPORT J, BABIKIAN V et al.: Reduction in stroke with gemfibrozil in men with coronary heart disease and low HDL cholesterol: The Veterans Affairs HDL Intervention Trial (VA-HIT). Circulation (2001) 103:2828–2833.
   PubMed Web of Science ®Google Scholar
• ERICSSON CG, NILSSON J, GRIP L, SVANE B, HAMSTEN A: Effect of bezafibrate treatment over five years on coronary plaques causing 20% to 50% diameter narrowing (The Bezafibrate Coronary Atherosclerosis Intervention Trial lBECAITD. Am. J. CardioL (1997) 80:1125–1129.
   PubMed Web of Science ®Google Scholar
• ERICSSON CG, HAMSTEN A, NILSSON J, GRIP L, SVANE B, DE FU: Angiographic assessment of effects of bezafibrate on progression of coronary artery disease in young male postinfarction patients. Lancet (1996) 347:849–853.
   PubMed Web of Science ®Google Scholar
• FRICK MH, SYVANNE M, NIEMINEN MS et al.: Prevention of the angiographic progression of coronary and vein-graft atherosclerosis by gemfibrozil after coronary bypass surgery in men with low levels of HDL cholesterol. Lopid Coronary Angiography Trial (LOCAT) Study Group. Circulation (1997) 96:2137–2143.
   PubMed Web of Science ®Google Scholar
• PETERS JM, AOYAMA T, BURNS AM, GONZALEZ FJ: Bezafibrate is a dual ligand for PPARalpha and PPARbeta: studies using null mice. Biochim. Biophys. Acta (2003) 1632:80–89.
   PubMed Web of Science ®Google Scholar
• SHI GQ, DROPINSKI JF, ZHANG Y et al.: Novel 2,3-dihydrobenzofuran-2-carboxylic acids: highly potent and subtype-selective PPARalpha agonists with potent hypolipidemic activity. J. Med. Chem. (2005) 48:5589–5599.
   PubMed Web of Science ®Google Scholar
• AUWERX J: PPARgamma, the ultimate thrifty gene. Diabetologia (1999) 42:1033–1049.
   PubMed Web of Science ®Google Scholar
• ••An excellent review of PPAR-regulated pathways including those involved in efficient energy storage.
   Google Scholar
• OTTO C, LEHRKE M, GOKE B: Novel insulin sensitizers: pharmacogenomic aspects. Pharmacogenomics (2002) 3:99–116.
   PubMed Web of Science ®Google Scholar
• SAKAMOTO J, KIMURA H, MORIYAMA S et al.: Activation of human peroxisome proliferator-activated receptor (PPAR) subtypes by pioglitazone. Biochem. Biophys. Res. Commun. (2000) 278:704–711.
   PubMed Web of Science ®Google Scholar
• KHAN MA, ST PJ, XUE JL: A prospective, randomized comparison of the metabolic effects of pioglitazone or rosiglitazone in patients with Type 2 diabetes who were previously treated with troglitazone. Diabetes Care (2002) 25:708–711.
   PubMed Web of Science ®Google Scholar
• YKI-JARVINEN H: Thiazolidinediones. N EngL J. Med. (2004) 351:1106–1118.
   PubMed Web of Science ®Google Scholar
• ••An excellent review of this drug class.
   Google Scholar
• GOLDBERG RB, KENDALL DM, DEEG MA et al.: A comparison of lipid and glycemic effects of pioglitazone and rosiglitazone in patients with Type 2 diabetes and dyslipidemia. Diabetes Care (2005) 28:1547–1554.
   PubMed Web of Science ®Google Scholar
• GERHOLD DL, LIU F, JIANG G et al.: Gene expression profile of adipocyte differentiation and its regulation by peroxisome proliferator-activated receptor-gamma agonists. Endocrinology (2002) 143:2106–2118.
   PubMed Web of Science ®Google Scholar
• PFUTZNER A, MARX N, LUBBEN G et al.: Improvement of cardiovascular risk markers by pioglitazone is independent from glycemic control: results from the pioneer study. J. Am. Coll. CardioL (2005) 45:1925–1931.
   PubMed Web of Science ®Google Scholar
• SATOH N, OGAWA Y, USUI T et al.: Antiatherogenic effect of pioglitazone in Type 2 diabetic patients irrespective of the responsiveness to its antidiabetic effect. Diabetes Care (2003) 26:2493–2499.
   PubMed Web of Science ®Google Scholar
• NAKAMURA T, MATSUDA T, KAWAGOE Y et al.: Effect of pioglitazone on carotid intima-media thickness and arterial stiffness in Type 2 diabetic nephropathy patients. Metabolism (2004) 53:1382–1386.
   PubMed Web of Science ®Google Scholar
• KOSHIYAMA H, SHIMONO D, KUWAMURA N, MINAMIKAWA J, NAKAMURA Y: Rapid communication: inhibitory effect of pioglitazone on carotid arterial wall thickness in Type 2 diabetes. J. Clin. EndocrinoL Metab (2001) 86:3452–3456.
   PubMed Web of Science ®Google Scholar
• LANGENFELD MR, FORST T, HOHBERG C et al.: Pioglitazone decreases carotid intima-media thickness independently of glycemic control in patients with Type 2 diabetes mellitus: results from a controlled randomized study. Circulation (2005) 111:2525–2531.
   PubMed Web of Science ®Google Scholar
• DORMANDY JA, CHARBONNEL B, ECKLAND DJ et al.: Secondary prevention of macrovascular events in patients with Type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet (2005) 366:1279–1289.
   PubMed Web of Science ®Google Scholar
• •A recent randomised clinical trial of pioglitazone.
   Google Scholar
• CHARBONNEL B, DORMANDY J, ERDMANN E, MASSI-BENEDETTI M, SKENE A: The prospective pioglitazone clinical trial in macrovascular events (PROactive): can pioglitazone reduce cardiovascular events in diabetes? Study design and baseline characteristics of 5238 patients. Diabetes Care (2004) 27: 1647-1653.
   Google Scholar
• SAAD MF, GRECO S, OSEI K et al.: Ragaglitazar improves glycemic control and lipid profile in Type 2 diabetic subjects: a 12-week, double-blind, placebo-controlled dose-ranging study with an open pioglitazone arm. Diabetes Care (2004) 27:1324–1329.
   PubMed Web of Science ®Google Scholar
• BRAND CL, STURIS J, GOTFREDSEN CF et al.: Dual PPARalpha /gamma activation provides enhanced improvement of insulin sensitivity and glycemic control in ZDF rats. Am. J. PhysioL EndocrinoL Metab (2003) 284:E841–E854.
   PubMed Web of Science ®Google Scholar
• PICKAVANCE LC, BRAND CL, WASSERMANN K, WILDING JP: The dual PPARalpha/gamma agonist, ragaglitazar, improves insulin sensitivity and metabolic profile equally with pioglitazone in diabetic and dietary obese ZDF rats. Br. J. PharmacoL (2005) 144:308–316.
   PubMed Web of Science ®Google Scholar
• OLIVER WR, JR., SHENK JL, SNAITH MR et al.: A selective peroxisome proliferator-activated receptor delta agonist promotes reverse cholesterol transport. Proc. NatL Acad. Sci. USA (2001) 98:5306–5311.
   Google Scholar
• WANG YX, LEE CH, TIEP S et al.: Peroxisome-proliferator-activated receptor delta activates fat metabolism to prevent obesity. Cell (2003) 113:159–170.
   PubMed Web of Science ®Google Scholar
• FLAVELL DM, PINEDA T, JAMSHIDI Y et al.: Variation in the PPARalpha gene is associated with altered function in vitro and plasma lipid concentrations in Type II diabetic subjects. Diabetologia (2000) 43:673–680.
   PubMed Web of Science ®Google Scholar
• TAI ES, CORELLA D, DEMISSIE S et al.: Polyunsaturated fatty acids interact with the PPARA-L162V polymorphism to affect plasma triglyceride and apolipoprotein C-III concentrations in the Framingham Heart Study./ Num (2005) 135:397–403.
   Google Scholar
• CHUANG LM, HSIUNG CA, CHEN YD et al.: Sibling-based association study of the PPARgamma2 Prol2Ala polymorphism and metabolic variables in Chinese and Japanese hypertension families: a SAPPHIRe study. Stanford Asian-Pacific Program in Hypertension and Insulin Resistance. J. Mo/. Med. (2001) 79:656–664.
   Google Scholar
• ANDRULIONYTE L, ZACHAROVA J, CHIASSON JL, LAAKSO M: Common polymorphisms of the PPAR-gamma2 (Prol2A1a) and PGC-lalpha (G1y4825er) genes are associated with the conversion from impaired glucose tolerance to Type 2 diabetes in the STOP-NIDDM trial. Diabetologia (2004) 47:2176–2184.
   PubMed Web of Science ®Google Scholar
• EK J, ANDERSEN G, URHAMMER SA et al.: Mutation analysis of peroxisome proliferator-activated receptor-gamma coactivator-1 (PGC-1) and relationships of identified amino acid polymorphisms to Type II diabetes mellitus. Diabetologia (2001) 44:2220–2226.
   PubMed Web of Science ®Google Scholar
• OSTERGARD T, EK J, HAMID Y et al.: Influence of the PPAR-gamma2 Prol2Ala and ACE I/D polymorphisms on insulin sensitivity and training effects in healthy offspring of Type 2 diabetic subjects. Horm. Metab. Res. (2005) 37:99–105.
   PubMed Web of Science ®Google Scholar
• SHIN HD, PARK BL, KIM LH et al.: Genetic polymorphisms in peroxisome proliferator-activated receptor delta associated with obesity. Diabetes (2004) 53:847–851.
   PubMed Web of Science ®Google Scholar
• SKOGSBERG J, KANNISTO K, CASSELTN, HAMSTEN A. ERIKSSON P, EHRENBORG E: Evidence that peroxisome proliferator-activated receptor delta influences cholesterol metabolism in men. Arterioscler. Thromb. Vase. Biol. (2003) 23:637–643.
   PubMed Web of Science ®Google Scholar
• RISTOW M, MULLER-WIELAND D, PFEIFFER A, KRONE W, KAHN CR: Obesity associated with a mutation in a genetic regulator of adipocyte differentiation. N EngL J. Med. (1998) 339:953–959.
   PubMed Web of Science ®Google Scholar
• NEMOTO M, SASAKI T, DEEB SS, FUJIMOTO WY, TAJIMA N: Differential effect of PPARgamma2 variants in the development of Type 2 diabetes between native Japanese and Japanese Americans. Diabetes Res.Clin. Pract. (2002) 57:131–137.
   PubMed Web of Science ®Google Scholar
• GONZALEZ SANCHEZ JL, SERRANO RM, FERNANDEZ PC, LAAKSO M, MARTINEZ LARRAD MT: Effect of the Prol2Ala polymorphism of the peroxisome proliferator-activated receptor gamma-2 gene on adiposity, insulin sensitivity and lipid profile in the Spanish population. Eur. J. EndocrinoL (2002) 147:495–501.
   PubMed Web of Science ®Google Scholar
• VOHL MC, LEPAGE P, GAUDET D et al.: Molecular scanning of the human PPARa gene: association of the L162v mutation with hyperapobetalipoproteinemia. J. Lipid Res. (2000) 41:945–952.
   PubMed Web of Science ®Google Scholar
• SAPONE k PETERS JM, SAKAI S et al.: The human peroxisome proliferator-activated receptor alpha gene: identification and functional characterization of two natural allelic variants. Pharmacogenetics (2000) 10:321–333.
   PubMedGoogle Scholar
• TAI ES, DEMISSIE S, CUPPLES LA et al.: Association between the PPARA L162V polymorphism and plasma lipid levels: the Framingham Offspring Study. Arterioscler. Thromb. Vase. Biol. (2002) 22:805–810.
   PubMed Web of Science ®Google Scholar
• FLAVELL DM, JAMSHIDI Y, HAWE E et al.: Peroxisome proliferator-activated receptor alpha gene variants influence progression of coronary atherosclerosis and risk of coronary artery disease. Circulation (2002) 105:1440–1445.
   PubMed Web of Science ®Google Scholar
• JAMSHIDI Y, MONTGOMERY HE, HENSE HW et al.: Peroxisome proliferator-activated receptor alpha gene regulates left ventricular growth in response o exercise and hypertension. Circulation (2002) 105:950–955.
   PubMed Web of Science ®Google Scholar
• •Demonstrates a significant association between PPARA intron 7 genotype and physiological and pathological left ventricular hypertrophy.
   Google Scholar
• SHER T, YT HF, MCBRIDE OW, GONZALEZ FJ: cDNA cloning, chromosomal mapping, and functional characterization of the human peroxisome proliferator activated receptor. Biochemistry (1993) 32:5598–5604.
   PubMed Web of Science ®Google Scholar
• MYERSON SG, MONTGOMERY HE, WHITTINGHAM M et al.: Left ventricular hypertrophy with exercise and ACE gene insertion/deletion polymorphism: a randomized controlled trial with losartan. Circulation (2001) 103:226–230.
   PubMed Web of Science ®Google Scholar
• SCHUNKERT H, HENGSTENBERG C, HOLMER SR et al.: Lack of association between a polymorphism of the aldosterone synthase gene and left ventricular structure. Circulation (1999) 99:2255–2260.
   PubMed Web of Science ®Google Scholar
• DEEB SS, FAJAS L, NEMOTO M et al.: A Prol2Ala substitution in PPARgamma2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity. Nat. Genet. (1998) 20:284–287.
   PubMed Web of Science ®Google Scholar
• PISCHON T, PAT JK, MANSON JE et al.: Peroxisome proliferator-activated receptor-gamma2 P12A polymorphism and risk of coronary heart disease in US men and women. Arterioscler. Thromb. Vase. Biol. (2005) 25:1654–1658.
   PubMed Web of Science ®Google Scholar
• DONEY AS, FISCHER B, LEESE G, MORRIS AD, PALMER CN: Cardiovascular risk in Type 2 diabetes is associated with variation at the PPARG locus: a Go-DARTS study. Arterioscler. Thromb. Vase. Biol. (2004) 24:2403–2407.
   PubMed Web of Science ®Google Scholar
• RIDKER PM, COOK NR, CHENG S et al.: Alanine for proline substitution in the peroxisome proliferator-activated receptor gamma-2 (PPARG2) gene and the risk of incident myocardial infarction. Arterioscler. Thromb. Vase. Biol. (2003) 23:859–863.
   PubMed Web of Science ®Google Scholar
• Final report on the aspirin component of the ongoing Physicians' Health Study. Steering Committee of the Physicians' Health Study Research Group. N EngL J. Med. (1989) 321:129–135.
   PubMed Web of Science ®Google Scholar
• IWATA E, YAMAMOTO I, MOTOMURA T et al.: The association of Prol2Ala polymorphism in PPARgamma2 with lower carotid artery IMT in Japanese. Diabetes Res. Clin. Pract. (2003) 62:55–59.
   PubMed Web of Science ®Google Scholar
• AL-SHALT KZ, HOUSE AA, HANLEY AJ et al: Genetic variation in PPARG encoding peroxisome proliferator-activated receptor gamma associated with carotid atherosclerosis. Stroke (2004) 35:2036–2040.
   PubMed Web of Science ®Google Scholar
• OSTGREN CJ, LINDBLAD U, BOG-HANSEN E, RANSTAM J, MELANDER A, RASTAM L: Differences in treatment and metabolic abnormalities between normo- and hypertensive patients with Type 2 diabetes: the Skaraborg Hypertension and Diabetes Project. Diabetes Obes. Metab. (1999) 1:105–112.
   PubMed Web of Science ®Google Scholar
• BOG-HANSEN E, LINDBLAD U, BENGTSSON K, RANSTAM J, MELANDER A, RASTAM L: Risk factor clustering in patients with hypertension and non-insulin-dependent diabetes mellitus. The Skaraborg Hypertension Project. J. Intern. Med. (1998) 243:223–232.
   Google Scholar
• OSTGREN CJ, LINDBLAD U, MELANDER O, MELANDER A, GROOP L, RASTAM L: Peroxisome proliferator-activated receptor-gammaProl2Ala polymorphism and the association with blood pressure in Type 2 diabetes: skaraborg hypertension and diabetes project. J. Hypertens. (2003) 21:1657–1662.
   PubMed Web of Science ®Google Scholar
• MEIRHAEGHE A, FAJAS L, HELBECQUE N et al.: A genetic polymorphism of the peroxisome proliferator-activated receptor gamma gene influences plasma leptin levels in obese humans. Hum. MoL Genet. (1998) 7:435–440.
   PubMed Web of Science ®Google Scholar
• WANG XL, OOSTERHOF J, DUARTE N: Peroxisome proliferator-activated receptor gamma C161- T polymorphism and coronary artery disease. Cardiovasc. Res. (1999) 44:588–594.
   PubMed Web of Science ®Google Scholar
• CHAO TH, LI YH, CHEN JH et al.: The 161TT genotype in the exon 6 of the peroxisome-proliferator-activated receptor gamma gene is associated with premature acute myocardial infarction and increased lipid peroxidation in habitual heavy smokers. Clin. Sci. (2004) 107:461–466.
   Web of Science ®Google Scholar
• SKOGSBERG J, KANNISTO K, ROSHANI L et al.: Characterization of the human peroxisome proliferator activated receptor delta gene and its expression. Int J. Mol Med. (2000) 6:73–81.
   PubMed Web of Science ®Google Scholar
• SKOGSBERG J, MCMAHON AD, KARPE F, HAMSTEN A, PACKARD CJ, EHRENBORG E: Peroxisome proliferator activated receptor delta genotype in relation to cardiovascular risk factors and risk of coronary heart disease in hypercholesterolaemic men. J. Intern. Med. (2003) 254:597–604.
   PubMed Web of Science ®Google Scholar
• TENKANEN L, MANTTARI M, MANNINEN V: Some coronary risk factors related to the insulin resistance syndrome and treatment with gemfibrozil. Experience from the Helsinki Heart Study. Circulation (1995) 92:1779–1785.
   PubMed Web of Science ®Google Scholar
• BOSSE Y, PASCOT A, DUMONT M et al.: Influences of the PPAR alpha-L162V polymorphism on plasma HDL(2)-cholesterol response of abdominally obese men treated with gemfibrozil. Genet. Med. (2002) 4:311–315.
   PubMed Web of Science ®Google Scholar
• JAMSHIDI Y, FLAVELL DM, HAWE E, MACCALLUM PK, MEADE TW, HUMPHRIES SE: Genetic determinants of the response to bezafibrate treatment in the lower extremity arterial disease event reduction (LEADER) trial. Atherosclerosis (2002) 163:183–192.
   PubMed Web of Science ®Google Scholar
• FOUCHER C, RATTIER S, FLAVELL DM et al: Response to micronized fenofibrate treatment is associated with the peroxisome-proliferator-activated receptors alpha G/C intron7 polymorphism in subjects with Type 2 diabetes. Pharmacogenetics (2004) 14:823–829.
   PubMedGoogle Scholar
• AZEN SP, PETERS RK, BERKOWITZ K, KJOS S, XIANG A, BUCHANAN TA: TRIPOD (TRoglitazone In the Prevention Of Diabetes): a randomized, placebo-controlled trial of troglitazone in women with prior gestational diabetes mellitus. Control. Clin. Trials (1998) 19:217–231.
   PubMedGoogle Scholar
• SNITKER S, WAANABE RM, ANI l et al.: Changes in insulin sensitivity in response to troglitazone do not differ between subjects with and without the common, functional Prol2Ala peroxisome proliferator-activated receptor-gamma2 gene variant: results from the Troglitazone in Prevention of Diabetes (TRIPOD) study. Diabetes Care (2004) 27:1365–1368.
   PubMed Web of Science ®Google Scholar
• KANG ES, PARK SY, KIM HJ et al.: Effects of Prol2Ala polymorphism of peroxisome proliferator-activated receptor gamma2 gene on rosiglitazone response in Type 2 diabetes. Clin. Pharmacol Ther. (2005) 78:202–208.
   PubMed Web of Science ®Google Scholar
• •Demonstrates significant association between PPARG Prol2Ala genotype and response to rosiglitazone.
   Google Scholar
• CHEN S, TSYBOULEVA N, BALLANTYNE CM, GOTTO AM, JR., MARIAN AJ: Effects of PPARalpha, gamma and delta haplotypes on plasma levels of lipids, severity and progression of coronary atherosclerosis and response to statin therapy in the lipoprotein coronary atherosclerosis study. Pharmacogenetics (2004) 14:61–71.
   Google Scholar