Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

Peroxisome Proliferator-Activated Receptor-γ

  • Elena SergeevaEmail author
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101879


Historical Background

As cardiovascular pathology and its complications are associated with metabolic and immunoregulative disorders, there is a more urgent need to understand the molecular basis of obesity, atherogenesis, and immune inflammation (Mangelsdorf 1995). The identification of peroxisome proliferator-activated receptor gamma (PPARγ) as a nuclear receptor, which has pleiotropic function in inflammation, cell growth and differentiation, apoptosis, and carbohydrate and fat metabolism, has offered new opportunities to understand and manipulate several key mechanisms of atherogenesis (Spiegelman et al. 1996; Clark 2002; Chen et al. 2003). The regulation of PPAR γ-dependent metabolic pathways and immune inflammation has enormous role in cardiovascular disease, metabolic syndrome, diabetes, and malignancy. It can also be important in immunological diseases like inflammatory bowel diseases, rheumatoid arthritis, multiple sclerosis, and psoriasis.


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  1. Ashok Kumar M, Veera Subhashini NG, Kanthimathi S, SaiBabu R, Ramesh A, Cherian KM, Emmanuel C. Associations for lipoprotein lipase and peroxisome proliferator-activated receptor-gamma gene and coronary artery disease in an Indian population. Arch Med Res. 2010;41(1):19–25. e1.CrossRefGoogle Scholar
  2. Bagi Z, Koller A, Kaley G. PPAR gamma activation, by reducing oxidative stress, increases NO bioavailability in coronary arterioles of mice with type 2 diabetes. Am J Physiol Heart Circ Physiol. 2004;286:H742–8.CrossRefPubMedGoogle Scholar
  3. Balakumara P, Rosea M, Singhb M. PPAR ligands: are they potential agents for cardiovascular disorders? Pharmacology. 2007;80:1–10.CrossRefGoogle Scholar
  4. Beamera BA, Negria C, Yen CJ, Gavrilova O. Chromosomal localization and partial genomic structure of the human peroxisome proliferator activated receptor-gamma (hPPARγ) gene. Biochem Biophys Res Commun. 1997;233(3):756–9.PubMedCrossRefGoogle Scholar
  5. Boyle PJ, King AB, Olansky L, Marchetti A, Lau H, Magar R, Martin J. Effects of pioglitazone and rosiglitazone on blood lipid levels and glycemic control in patients with type 2 diabetes mellitus: a retrospective review of randomly selected medical records. Clin Ther. 2002;24(3):378–96.CrossRefPubMedGoogle Scholar
  6. Chao L, Marcus-Samuels B, Mason MM, Moitra J, Vinson C, Arioglu E, Gavrilova O, Reitman ML. Adipose tissue is required for the antidiabetic, but not for the hypolipidemic, effect of thiazolidinediones. J Clin Invest. 2000;106:1221–8.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Chawla A. Control of macrophage activation and function by PPARs. Circ Res. 2010;106:1559.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Chawla A, Schwarz EJ, Dimaculangan DD, Lazar MA. Peroxisome proliferator-activated receptor (PPAR) gamma: adipose-predominant expression and induction early in adipocyte differentiation. Endocrinology. 1994;135:798–800.CrossRefPubMedGoogle Scholar
  9. Chawla A, Barak Y, Nagy L, Liao D, Tontonoz P, Evans RM. PPAR-gamma dependent and independent effects on macrophage-gene expression in lipid metabolism and inflammation. Nat Med. 2001a;7(1):48–52.CrossRefPubMedGoogle Scholar
  10. Chawla A, Barak Y, Nagy L, Tontonoz P, et al. A PPARγ-LXR-ABCA1 pathway in macrophages is involved in cholesterol efflux and atherogenesis. Mol Cell. 2001b;7(1):161–71.CrossRefPubMedGoogle Scholar
  11. Chen YE, Fu M, Zhang J, Zhu X, Lin Y, Akinbami MA, Song Q. Peroxisome proliferator-activated receptors and the cardiovascular system. Vitam Horm. 2003;66:157–88.CrossRefPubMedGoogle Scholar
  12. Chistiakov DA, Potapov VA, Khodirev DS et al. The PPARgamma Pro12Ala variant is associated with insulin sensitivity in Russian normoglycaemic and type 2 diabetic subjects. 2010 Diab Vasc Dis Res Jan;7(1):56–62.Google Scholar
  13. Choi D, Kim S-K, Choi S-H, Ko Y-G, Ahn C-W, Jang Y, Lim S-K, Lee H-C, Cha B-S. Preventative effects of rosiglitazone on restenosis after coronary stent implantation in patients with type 2 diabetes. Diabetes Care. 2004;27:2654–60.CrossRefPubMedGoogle Scholar
  14. Clark RB. The role of PPARs in inflammation and immunity. J Leukoc Biol. 2002;71(3):388–400.PubMedGoogle Scholar
  15. Clark RB, Bishop-Bailey D, Estrada-Hernandez T, Hla T, Puddington L, Padula SJ. The nuclear receptor PPARγ and immunoregulation: PPARγ mediates inhibition of helper T cell responses. J Immunol. 2000;164(3):1364–71.CrossRefPubMedGoogle Scholar
  16. de Dios ST, Bruemmer D, Dilley RJ, Ivey ME, Jennings GL, Law RE, Little PJ. Inhibitory activity of clinical thiazolidinedione peroxisome proliferator activating receptor-gamma ligands toward internal mammary artery, radial artery, and saphenous vein smooth muscle cell proliferation. Circulation. 2003;107:2548–50.CrossRefPubMedGoogle Scholar
  17. del Río LA, Sandalio LM, Palma JM, Bueno P, Corpas FJ. Metabolism of oxygen radicals in peroxisomes and cellular implications. Free Radic Biol Med. 1992;13(5):557–80.CrossRefPubMedGoogle Scholar
  18. Desouza CV, Murthy SN, Diez J, Dunne B, Matta AS, Fonseca VA, McNamara DB. Differential effects of peroxisome proliferator activator receptor-alpha and gamma ligands on intimal hyperplasia after balloon catheter-induced vascular injury in Zucker rats. J Cardiovasc Pharmacol Ther. 2003;8:297–305.CrossRefPubMedGoogle Scholar
  19. Desreumaux P, Dubuquoy L, Nutten S, et al. Attenuation of colon inflammation through activators of the retinoid X receptor (RXR)/peroxisome proliferator-activated receptor γ (PPARγ) heterodimer: a basis for new therapeutic strategies. J Exp Med. 2001;193(7):827–38.PubMedPubMedCentralCrossRefGoogle Scholar
  20. Desvergne B, Wahli W. Peroxisome proliferator-activated receptors: nuclear control of metabolism. Endocr Rev. 1999;20:649–88.PubMedGoogle Scholar
  21. Dubey RK, Zhang HY, Reddy SR, Boegehold MA, Kotchen TA. Pioglitazone attenuates hypertension and inhibits growth of renal arteriolar smooth muscle in rats. Am J Phys. 1993;265:R726–32.Google Scholar
  22. Ellis CN, Varani J, Fisher GJ, et al. Troglitazone improves psoriasis and normalizes models of proliferative skin disease: ligands for peroxisome proliferator-activated receptor-γ inhibit keratinocyte proliferation. Arch Dermatol. 2000;136(5):609–16.CrossRefPubMedGoogle Scholar
  23. Fajas L, Fruchart JC, Auwerx J. PPARγ3 mRNA: a distinct PPARγ mRNA subtype transcribed from an independent promoter. FEBS Lett. 1998;438(1–2):55–60.CrossRefPubMedGoogle Scholar
  24. Feinstein DL, Galea E, Gavrilyuk V, et al. Peroxisome proliferator-activated receptor-γ agonists prevent experimental autoimmune encephalomyelitis. Ann Neurol. 2002;51(6):694–702.CrossRefPubMedGoogle Scholar
  25. Fisher JS, Gao J, Han DH, Holloszy JO, Nolte LA. Activation of AMP kinase enhances sensitivity of muscle glucose transport to insulin. Am J Physiol Endocrinol Metab. 2002;282:E18–23.CrossRefPubMedGoogle Scholar
  26. Forman BM, Tontonoz P, Chen J, Brun RP, Spiegelman BM, Evans RM. 15-deoxy-Δ12,14-prostaglandin J2 is a ligand for the adipocyte determination factor PPARγ. Cell. 1995;83(5):803–12.CrossRefPubMedGoogle Scholar
  27. Fryer LG, Parbu-Patel A, Carling D. The anti-diabetic drugs rosiglitazone and metformin stimulate AMP-activated protein kinase through distinct signaling pathways. J Biol Chem. 2002;277:25226–32.CrossRefPubMedGoogle Scholar
  28. Gao L, Wang L, Yun H, Su L, Su X. Association of the PPARgamma2 gene Pro12Ala variant with primary hypertension and metabolic lipid disorders in Han Chinese of Inner Mongolia. Genet Mol Res. 2010;9(3):1312–20.CrossRefPubMedGoogle Scholar
  29. Garg A. Acquired and inherited lipodystrophies. N Engl J Med. 2004;350:1220–34.CrossRefPubMedGoogle Scholar
  30. Gilroy DW, Colville-Nash PR, Chivers WJ, Paul-Clark MJ, Willoughby DA. Inducible cyclooxygenase may have anti-inflammatory properties Nat. Nat Med. 1999;5(6):698–708.CrossRefPubMedGoogle Scholar
  31. Gosset P, Charbonnier A-S, Delerive P, et al. Peroxisome proliferator-activated receptor γ activators affect the maturation of human monocyte-derived dendritic cells. Eur J Immunol. 2001;31(10):2857–65.CrossRefPubMedGoogle Scholar
  32. Graf K, Xi XP, Hsueh WA, Law RE. Troglitazone inhibits angiotensin II-induced DNA synthesis and migration in vascular smooth muscle cells. FEBS Lett. 1997;400:119–21.CrossRefPubMedGoogle Scholar
  33. Greene ME, Blumberg B, McBride OW, Yi HF, Kronquist K, Hsieh L, Greene G, Nimer SD. Isolation of the human peroxisome proliferator activated receptor γ cDNA: expression in hematopoietic cells and chromosomal mapping. Gene Expr. 1995;4:281–99.PubMedGoogle Scholar
  34. Han KH, Chang MK, Boullier A, Green SR, Li A, Glass CK, Quehenberger O. Oxidized LDL reduces monocyte CCR2 expression through pathways involving peroxisome proliferator-activated receptor γ. J Clin Invest. 2000;106:793–802.PubMedPubMedCentralCrossRefGoogle Scholar
  35. Hoepfner D, Schildknegt D, Braakman I, Philippsen P, Tabak HF. Contribution of the endoplasmic reticulum to peroxisome formation. Cell. 2005;122(1):85–95.CrossRefPubMedGoogle Scholar
  36. Hsueh WA, Jackson S, Law RE. Control of vascular cell proliferation and migration by PPAR-γ: a new approach to the macrovascular complications of diabetes (Review). Diabetes Care. 2001;24:392–7.CrossRefPubMedGoogle Scholar
  37. Issemann I, Green S. Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature. 1990;347(6294):645–50.CrossRefPubMedGoogle Scholar
  38. Jeong HW, Joo WL, Woo SK, et al. A non-TZD PPARα/γ dual agonist CG301360 alleviates insulin resistance and lipid dysregulation in db/db mice. Mol Pharmacol. 2010;78(5):877–85.CrossRefPubMedGoogle Scholar
  39. Ji Y, Liu J, et al. PPARγ agonist, rosiglitazone, regulates angiotensin II-induced vascular inflammation through the TLR4-dependent signaling pathway. Lab Investig. 2009;89:887–902.CrossRefPubMedGoogle Scholar
  40. Jiang C, Ting AT, Seed B. PPAR-γ agonists inhibit production of monocyte inflammatory cytokines. Nature. 1998;391(6662):82–6.CrossRefPubMedGoogle Scholar
  41. Kipshidze N, Dangas G, Tsapenko M, Moses J, Leon MB, Kutryk M, Serruys P. Role of the endothelium in modulating neointimal formation: vasculoprotective approaches to attenuate restenosis after percutaneous coronary interventions. J Am Coll Cardiol. 2004;44:733–9.PubMedGoogle Scholar
  42. Kliewer SA, Lenhard JM, Willson TM, Patel I, Morris DC, Lehmann JM. A prostaglandin J2 metabolite binds peroxisome proliferator-activated receptor γ and promotes adipocyte differentiation. Cell. 1995;83(5):813–9.CrossRefPubMedGoogle Scholar
  43. Kliewer SA, Moore JT, Wade L, et al. An orphan nuclear receptor activated by pregnanes defines a novel steroid signaling pathway. Cell. 1998;92:73–82.CrossRefPubMedGoogle Scholar
  44. Kliewer SA, Xu HE, Lambert MH, Willson TM. Peroxisome proliferators-activated receptors. From genes to physiology. Recent Prog Horm Res. 2001;56:239–65.CrossRefPubMedGoogle Scholar
  45. Klinge CM, Bodenner DL. Binding of type II nuclear receptors and estrogen receptor to full and half-site estrogen response elements in vitro. Nucleic Acids Res. 1997;25(10):1903–12.PubMedPubMedCentralCrossRefGoogle Scholar
  46. Komar CM. Peroxisome proliferator-activated receptors (PPARs) and ovarian function--implications for regulating steroidogenesis, differentiation, and tissue remodeling. Reprod Biol Endocrinol. 2005;3:41.PubMedPubMedCentralCrossRefGoogle Scholar
  47. Komatsu A, Node K. Effects of PPARgamma agonist on dyslipidemia and atherosclerosis. Nippon Rinsho. 2010;68(2):294–8.PubMedGoogle Scholar
  48. Kubota N, Terauchi Y, Miki H, et al. PPARγ mediates high-fat diet–induced adipocyte hypertrophy and insulin resistance. Mol Cell. 1999;4(4):597–609.CrossRefPubMedGoogle Scholar
  49. Law RE, Meehan WP, Xi XP, Graf K, Wuthrich DA, Coats W, Faxon D, Hsueh WA. Troglitazone inhibits vascular smooth muscle cellgrowth and intimal hyperplasia. J Clin Invest. 1996;98:1897–905.PubMedPubMedCentralCrossRefGoogle Scholar
  50. Law RE, Goetze S, Xi XP, Jacksonn S, Kawano Y, Demer L, Fishbein MC, Meehan WP, Hsueh WA. Expression and function of PPAR-γ in rat and human vascular smooth muscle cells. Circulation. 2000;101:1311–8.CrossRefPubMedGoogle Scholar
  51. Lefebvre A, Chen I, Desreumaux P, Najib J, Fruchart J, Geboes K, Briggs M, Heyman R, Auwerx J. Activation of the peroxisome prolifertor-activated receptor-γ promotes the development of colon tumors in C57BL/6j–APCmin/+ mice. Nat Med. 1998;4:1053–7.CrossRefPubMedGoogle Scholar
  52. Lehrke M, Lazar MA. The many faces of PPARgamma. Cell. 2005;123:993–9.CrossRefPubMedPubMedCentralGoogle Scholar
  53. Liu XL, Zhang FL, Zhou ZY, Zhao HL, Shen GM, Baohan WY, Duan ZY, Li W, Zhang JW. Analysis of two sequence variants in peroxisome proliferator activated receptor gamma gene in Tajik population at high altitudes and Han population at low altitudes in China. Mol Biol Rep. 2010;37(1):179–84.CrossRefPubMedGoogle Scholar
  54. Maeda N, Takahashi M, Funahashi T, Kihara S, Nishizawa H, Kishida K, Nagaretani H, Matsuda M, Komuro R, Ouchi N, Kuriyama H, Hotta K, Nakamura T, Shimomura I, Matsuzawa Y. PPARgamma ligands increase expression and plasma concentrations of adiponectin, an adipose-derived protein. Diabetes. 2001;50:2094–9.PubMedCrossRefGoogle Scholar
  55. Mangelsdorf DJ, Thummel C, Beato M, Herrlich P, et al. The nuclear receptor superfamily. Cell. 1995;83:835–9.CrossRefPubMedPubMedCentralGoogle Scholar
  56. Marika J, Linja MJ, Porkka KP. Expression of androgen receptor coregulators in prostate cancer. Clin Cancer Res. 2004;10:1032–40.CrossRefGoogle Scholar
  57. Marx N, Schonbeck U, Lazar MA, Libby P, Plutzky J. Peroxisome proliferator-activated receptor γ activators inhibit gene expression and migration in human vascular smooth muscle cells. Circ Res. 1998;83:1097–103.PubMedPubMedCentralCrossRefGoogle Scholar
  58. Marx N, Froehlich J, et al. Antidiabetic PPAR{gamma}-activator rosiglitazone reduces MMP-9 serum levels in type 2 diabetic patients with coronary artery disease. Arterioscler Thromb Vasc Biol. 2003a;23:283–8.CrossRefPubMedGoogle Scholar
  59. Marx N, Imhof A, Froehlich J, et al. Effect of rosiglitazone treatment on soluble CD40L in patients with type 2 diabetes and coronary artery disease. Circulation. 2003b;107:1954–7.CrossRefPubMedGoogle Scholar
  60. Marx N, Wöhrle J, Nusser T, et al. Pioglitazone reduces neointima volume after coronary stent implantation. A randomized, placebo-controlled, double-blind trial in nondiabetic patients. Circulation. 2005;112:2792–8.CrossRefPubMedGoogle Scholar
  61. Minamikawa J, Tanaka S, Yamauchi M, Inoue D, Koshiyama H. Potent inhibitory effect of troglitazone on carotid arterial wall thickness in type 2 diabetes. J Clin Endocrinol Metab. 1998;83:1818–20.CrossRefPubMedGoogle Scholar
  62. Nassar B.A., Kenneth R., Susan A. K, Thomas P. R. et al. Improved prediction of early-onset coronary artery disease using APOE ε4, BChE-K, PPARγ2 Pro12 and ENOS T-786C in a polygenic model. Clin Biochem: vol 39, Issue 2, February 2006, Pp 109–114.PubMedCrossRefGoogle Scholar
  63. Novac N, Heinzel T. Nuclear receptors: overview and classification. Curr Drug Targets Inflamm Allergy. 2004;3(4):335–46.CrossRefPubMedGoogle Scholar
  64. Okuno A, Tamemoto H, Tobe K, Ueki K, Iwamoto K, Mori Y, Umesono K, Akanuma Y, Fujiwara T, Horikoshi H, et al. Troglitazone increases the number of small adipocytes without the change of white adipose tissue mass in obese Zucker rats. J Clin Invest. 1998;101:1354–61.PubMedPubMedCentralCrossRefGoogle Scholar
  65. Padilla J, Leung E, Phipps RP. Human B lymphocytes and B lymphomas express PPAR-γ and are killed by PPAR-γ agonists. Clin Immunol. 2002;103(1):22–33.CrossRefPubMedGoogle Scholar
  66. Peng D-Q, Zhao S-P, Nie S, Li J. Gene–gene interaction of PPARγ and ApoE affects coronary heart disease risk. Int J Cardiol. 2003;92(2):257–63.CrossRefPubMedGoogle Scholar
  67. Pischon T., Pai J.K., Manson J.E., Hu F.B., Rexrode K.M. Peroxisome proliferator-activated receptor-gamma2 P12A polymorphism and risk of coronary heart disease in US men and women. Arterioscler Thromb Vasc Biol. 2005. Vol. 25:1654–1658.CrossRefPubMedGoogle Scholar
  68. Plutzky J. Atherosclerotic plaque rupture: emerging insights and opportunities. Am J Cardiol. 1999;84:15J–20J.CrossRefPubMedGoogle Scholar
  69. Ricote M, Huang J, Fajas L, et al. Expression of the peroxisome proliferator-activated receptor γ (PPARγ) in human atherosclerosis and regulation in macrophages by colony stimulating factors and oxidized low density lipoprotein. Proc Natl Acad Sci USA. 1998;95(13):7614–9.PubMedPubMedCentralCrossRefGoogle Scholar
  70. Rodriguez S.R. et al., Different effects of thiazolidinediones on cardiovascular risk in patients with type 2 diabetes mellitus: pioglitazone vs rosiglitazone, Curr Drug Saf volume 5, N. 3, July 2010 , pp. 234–244.Google Scholar
  71. Ruderman N, Prentki M. AMP kinase and malonyl-CoA: targets for therapy of the metabolic syndrome. Nat Rev Drug Discov. 2004;3:340–51.CrossRefPubMedGoogle Scholar
  72. Sabatino L, Casamassimi A. A novel peroxisome proliferator-activated receptor γ isoform with dominant negative activity generated by alternative splicing. J Biol Chem. 2005;280(28):26517–25.CrossRefPubMedGoogle Scholar
  73. Saha AK, Avilucea PR, Ye JM, Assifi MM, Kraegen EW, Ruderman NB. Pioglitazone treatment activates AMP-activated protein kinase in rat liver and adipose tissue in vivo. Biochem Biophys Res Commun. 2004;314:580–5.CrossRefPubMedGoogle Scholar
  74. Schneider JG, Schiekofer S, von Eynatten M, Dugi KA. PPAR gamma variant influences angiographic outcome and 10-year cardiovascular risk in male symptomatic coronary artery disease patients: response to Regieli et al. Diabetes Care. 2009 Jun;32(6):e75; author reply e76. doi: 10.2337/dc09-0393.CrossRefPubMedGoogle Scholar
  75. Sergeeva EG, Berkovich OA, Ionova ZI, Ptchelina SM, Zaraisky MI and Carpenko MA Association of peroxisome proliferator-activated receptor- gamma2 Pro12Ala gene variants with insulinoresistance in coronary heart disease patients J. Heart and Stroke. 2017;2(1) Article 1016.Google Scholar
  76. Setoguchi K, Misaki Y, Terauchi Y, et al. Peroxisome proliferator-activated receptor-γ haploinsufficiency enhances B cell proliferative responses and exacerbates experimentally induced arthritis. J Clin Investig. 2001;108(11):1667–75.PubMedPubMedCentralCrossRefGoogle Scholar
  77. Sidhu JS, Cowan D, et al. The effects of rosiglitazone, a peroxisome proliferator-activated receptor-gamma agonist, on markers of endothelial cell activation, C-reactive protein, and fibrinogen levels in non-diabetic coronary artery disease patients. J Am Coll Cardiol. 2003;42(10):1757–63.CrossRefPubMedGoogle Scholar
  78. Sidhu JS, Kaposzta Z, Markus HS, Kaski JC. Effect of rosiglitazone on common carotid intima-media thickness progression in coronary artery disease patients without diabetes mellitus. Arterioscler Thromb Vasc Biol. 2004;24:930–4.CrossRefPubMedGoogle Scholar
  79. Spiegelman BM, et al. Adipogenesis and obesity: rounding out the big picture. Cell. 1996;87:337–89.CrossRefGoogle Scholar
  80. Staels B, Fruchart JC. Therapeutic roles of peroxisome proliferator-activated receptor agonists. Diabetes. 2005;54(8):2460–70.CrossRefPubMedGoogle Scholar
  81. Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, Patel HR, Ahima RS, Lazar MA. The hormone resistin links obesity to diabetes. Nature. 2001;409:307–12.CrossRefPubMedGoogle Scholar
  82. Sutton M, Rendell M, Dandona P, Dole JF, Murphy K, Patwardhan R, Patel J, Freed M. A comparison of the effects of rosiglitazone and glyburide on cardiovascular function and glycemic control in patients with type 2 diabetes. Diabetes Care. 2002;25:2058–64.CrossRefGoogle Scholar
  83. Takagi T, Yamamuro A, Tamita K, Yamabe K, Katayama M, Mizoguchi S, Ibuki M, Tani T, Tanabe K, Nagai K, Shiratori K, Morioka S, Yoshikawa J. Pioglitazone reduces neointimal tissue proliferation after coronary stent implantation in patients with type 2 diabetes mellitus: an intravascular ultrasound scanning study. Am Heart J. 2003;146:E5.CrossRefPubMedGoogle Scholar
  84. Tontonoz P, Hu E, Spiegelman BM. Stimulation of adipogenesis in fibroblasts by PPARγ2, a lipid-activated transcription factor. Cell. 1994a;79(7):1147–56.CrossRefPubMedGoogle Scholar
  85. Tontonoz P, Graves RA, Budavari AI, Erdjument-Bromage H, Lui M, Hu E, Tempst P, Spiegelman BM. Adipocyte-specific transcription factor ARF6 is a heterodimeric complex of two nuclear hormone receptors, PPAR gamma and RXR alpha. Nucleic Acids Res. 1994b;22:5628–34.PubMedPubMedCentralCrossRefGoogle Scholar
  86. Tontonoz P, Laszlo N, Jacqueline GA, Thomazy VA, Ronald ME. PPARγ promotes monocyte/macrophage differentiation and uptake of oxidized LDL. Cell. 1998;93(2):241–52.CrossRefPubMedGoogle Scholar
  87. Touyz RM, Schiffrin EL. Review Peroxisome proliferator-activated receptors in vascular biology-molecular mechanisms and clinical implications. Vasc Pharmacol. 2006;45(1):19–28.CrossRefGoogle Scholar
  88. Ulivieri C, Baldari CT. The potential of PPARgamma ligands in the treatment of hematological malignancies. Mini-Rev Med Chem. 2007;7(9):877–87.CrossRefPubMedGoogle Scholar
  89. Chatterjee VKK. PPAR gamma and human insulin resistance. Soc Endocrinol. 2001; 2.Google Scholar
  90. Vogel U, Segel S, Dethlefsen C, Tjønneland A, Saber AT, Wallin H, Jensen MK, Schmidt EB, Andersen PS, Overvad K. 2009 ‘PPAR gamma Pro(12)Ala polymorphism and risk of acute coronary syndrome in a prospective study of Danes’ BMC Medical Genetics, vol 10. DOI: 10.1186/1471-2350-10-52.Google Scholar
  91. Wang CH, Ciliberti N, Li SH, Szmitko PE, Weisel RD, Fedak PW, Al Omran M, Cherng WJ, Li RK, Stanford WL, Verma S. Rosiglitazone facilitates angiogenic progenitor cell differentiation toward endothelial lineage: a new paradigm in glitazone pleiotropy. Circulation. 2004a;109:1392–400.CrossRefPubMedGoogle Scholar
  92. Wang TD, Chen WJ, Lin JW, Chen MF, Lee YT. Effects of rosiglitazone on endothelial function, C-reactive protein, and components of the metabolic syndrome in nondiabetic patients with the metabolic syndrome. Am J Cardiol. 2004b;93:362–5.CrossRefPubMedGoogle Scholar
  93. Watanabe H, Nakagawa K, Kakihana M. Effects of peroxisome proliferator-activated receptor (PPAR) ligands on vascular function in patients with the metabolic syndrome. Circulation. 2006;114:880.Google Scholar
  94. Willson TM, Jeffery EC, David JC, Robert WW, et al. The structure-activity relationship between peroxisome proliferator-activated receptor γ agonism and the antihyperglycemic activity of thiazolidinediones. J Med Chem. 1996;39(3):665–8.CrossRefPubMedGoogle Scholar
  95. Wortham M, Czerwinski M. Expression of constitutive androstane receptor, hepatic nuclear factor 4 alpha, and P450 oxidoreductase genes determines interindividual variability in basal expression and activity of a broad scope of xenobiotic metabolism genes in the human liver. Drug Metab Dispos. 2007;35(9):1700–10.CrossRefPubMedGoogle Scholar
  96. Xin X, Yang S, Kowalski J, Gerritsen ME. Peroxisome proliferator-activated receptor γ ligands are potent inhibitors of angiogenesis in vitro and in vivo. J Biol Chem. 1999;274:9116–21.CrossRefPubMedGoogle Scholar
  97. Yang XY, Wang LH, Mihalic K, Xiao W, Chen T, Li P, Wahl LM, Farrar WL. Interleukin (IL)-4 indirectly suppresses IL-2 production by human T lymphocytes via peroxisome proliferator-activated receptor gamma activated by macrophage-derived 12/15-lipoxygenase ligands. J Biol Chem. 2002;277:3973–8.CrossRefPubMedGoogle Scholar
  98. Zang C, Liu H, Waechter M, et al. Dual PPARα/γ ligand TZD18 either alone or in combination with imatinib inhibits proliferation and induces apoptosis of human CML cell lines. Cell Cycle. 2006;5(19):2237–43.CrossRefPubMedGoogle Scholar
  99. Zhang L, Xie P, Wang J, Yang Q, Fang C, Zhou S, Li J. Impaired peroxisome proliferator-activated receptor-γ contributes to phenotypic modulation of vascular smooth muscle cells during hypertension. J Biol Chem. 2010;285:13666–77.PubMedPubMedCentralCrossRefGoogle Scholar
  100. Zhu Y, Alvares K, Huang Q, Rao MS, Reddy JK. Cloning of a new member of the peroxisome proliferatoractivated receptor gene family from mouse liver. J Biol Chem. 1993;268:26817–20.PubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.I.P. Pavlov 1st Saint Petersburg State Medical UniversitySt. PetersburgRussia
  2. 2.Federal Almazov North-West Research CentreSt. PetersburgRussia