Nutrition, Metabolism & Cardiovascular Diseases
Volume 19, Issue 11 , Pages 751-759 , December 2009

Peroxisome proliferator-activated receptors and angiogenesis

  • F. Biscetti

      Affiliations

    • Laboratory of Vascular Biology and Genetics, Department of Medicine, A. Gemelli University Hospital, Catholic University School of Medicine, Largo F. Vito, 8, 00168 Rome, Italy
    • Corresponding Author InformationCorresponding author. Tel.: +39 06 3015 4518; fax: +39 06 3550 0486.
  • ,
  • G. Straface

      Affiliations

    • Unit of Vascular Medicine and Mass Spectrometry Laboratory, Department of Experimental Medicine, Polo Pontino Sapienza University of Rome, Corso della Repubblica, 79, 04100 Latina, Italy
  • ,
  • D. Pitocco

      Affiliations

    • Laboratory of Vascular Biology and Genetics, Department of Medicine, A. Gemelli University Hospital, Catholic University School of Medicine, Largo F. Vito, 8, 00168 Rome, Italy
  • ,
  • F. Zaccardi

      Affiliations

    • Laboratory of Vascular Biology and Genetics, Department of Medicine, A. Gemelli University Hospital, Catholic University School of Medicine, Largo F. Vito, 8, 00168 Rome, Italy
  • ,
  • G. Ghirlanda

      Affiliations

    • Laboratory of Vascular Biology and Genetics, Department of Medicine, A. Gemelli University Hospital, Catholic University School of Medicine, Largo F. Vito, 8, 00168 Rome, Italy
  • ,
  • A. Flex

      Affiliations

    • Laboratory of Vascular Biology and Genetics, Department of Medicine, A. Gemelli University Hospital, Catholic University School of Medicine, Largo F. Vito, 8, 00168 Rome, Italy

Received 23 December 2008 ,Revised 15 March 2009 ,Accepted 20 April 2009.

References 

  1. Lemay DG, Hwang DH. Genome-wide identification of peroxisome proliferator response elements using integrated computational genomics. J Lipid Res. 2006;47(7):1583–1587
  2. Simons M. Angiogenesis: where do we stand now?. Circulation. 2005;111(12):1556–1566
  3. Kota BP, Huang TH, Roufogalis BD. An overview on biological mechanisms of PPARs. Pharmacol Res. 2005;51(2):85–94
  4. Berger J, Moller DE. The mechanisms of action of PPARs. Annu Rev Med. 2002;53:409–435
  5. Braissant O, Wahli W. Differential expression of peroxisome proliferator-activated receptor-alpha, -beta, and -gamma during rat embryonic development. Endocrinology. 1998;139(6):2748–2754
  6. Auboeuf D, Rieusset J, Fajas L, Vallier P, Frering V, Riou JP, et al. Tissue distribution and quantification of the expression of mRNAs of peroxisome proliferator-activated receptors and liver X receptor-alpha in humans: no alteration in adipose tissue of obese and NIDDM patients. Diabetes. 1997;46(8):1319–1327
  7. Chinetti G, Griglio S, Antonucci M, Torra IP, Delerive P, Majd Z, et al. Activation of proliferator-activated receptors alpha and gamma induces apoptosis of human monocyte-derived macrophages. J Biol Chem. 1998;273(40):25573–25580
  8. 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(2):370–374
  9. Staels B, Koenig W, Habib A, Merval R, Lebret M, Torra IP, et al. Activation of human aortic smooth-muscle cells is inhibited by PPARalpha but not by PPARgamma activators. Nature. 1998;393(6687):790–793
  10. Fajas L, Auboeuf D, Raspe E, Schoonjans K, Lefebvre AM, Saladin R, et al. The organization, promoter analysis, and expression of the human PPARgamma gene. J Biol Chem. 1997;272(30):18779–18789
  11. Greene ME, Blumberg B, McBride OW, Yi HF, 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. 1995;4(4–5):281–299
  12. Zhu Y, Qi C, Korenberg JR, Chen XN, Noya D, Rao MS, et al. Structural organization of mouse peroxisome proliferator-activated receptor gamma (mPPAR gamma) gene: alternative promoter use and different splicing yield two mPPAR gamma isoforms. Proc Natl Acad Sci U S A. 1995;92(17):7921–7925
  13. Elbrecht A, Chen Y, Cullinan CA, Hayes N, Leibowitz M, Moller DE, et al. Molecular cloning, expression and characterization of human peroxisome proliferator activated receptors gamma 1 and gamma 2. Biochem Biophys Res Commun. 1996;224(2):431–437
  14. Kliewer SA, Forman BM, Blumberg B, Ong ES, Borgmeyer U, Mangelsdorf DJ, et al. Differential expression and activation of a family of murine peroxisome proliferator-activated receptors. Proc Natl Acad Sci U S A. 1994;91(15):7355–7359
  15. Mukherjee R, Jow L, Noonan D, McDonnell DP. Human and rat peroxisome proliferator activated receptors (PPARs) demonstrate similar tissue distribution but different responsiveness to PPAR activators. J Steroid Biochem Mol Biol. 1994;51(3–4):157–166
  16. Yoshikawa T, Brkanac Z, Dupont BR, Xing GQ, Leach RJ, Detera-Wadleigh SD. Assignment of the human nuclear hormone receptor, NUC1 (PPARD), to chromosome 6p21.1–p21.2. Genomics. 1996;35(3):637–638
  17. Jones PS, Savory R, Barratt P, Bell AR, Gray TJ, Jenkins NA, et al. Chromosomal localisation, inducibility, tissue-specific expression and strain differences in three murine peroxisome-proliferator-activated-receptor genes. Eur J Biochem. 1995;233(1):219–226
  18. 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(5):2367–2371
  19. Xu HE, Lambert MH, Montana VG, Parks DJ, Blanchard SG, Brown PJ, et al. Molecular recognition of fatty acids by peroxisome proliferator-activated receptors. Mol Cell. 1999;3(3):397–403
  20. Forman BM, Tontonoz P, Chen J, Brun RP, Spiegelman BM, Evans RM. 15-Deoxy-delta 12, 14-prostaglandin J2 is a ligand for the adipocyte determination factor PPAR gamma. Cell. 1995;83(5):803–812
  21. Davies SS, Pontsler AV, Marathe GK, Harrison KA, Murphy RC, Hinshaw JC, et al. Oxidized alkyl phospholipids are specific, high affinity peroxisome proliferator-activated receptor gamma ligands and agonists. J Biol Chem. 2001;276(19):16015–16023
  22. Forman BM, Chen J, Evans RM. Hypolipidemic drugs, polyunsaturated fatty acids, and eicosanoids are ligands for peroxisome proliferator-activated receptors alpha and delta. Proc Natl Acad Sci U S A. 1997;94(9):4312–4317
  23. Yu K, Bayona W, Kallen CB, Harding HP, Ravera CP, McMahon G, et al. Differential activation of peroxisome proliferator-activated receptors by eicosanoids. J Biol Chem. 1995;270(41):23975–23983
  24. Hess R, Staubli W, Riess W. Nature of the hepatomegalic effect produced by ethyl-chlorophenoxy-isobutyrate in the rat. Nature. 1965;208(5013):856–858
  25. Staels B, Dallongeville J, Auwerx J, Schoonjans K, Leitersdorf E, Fruchart JC. Mechanism of action of fibrates on lipid and lipoprotein metabolism. Circulation. 1998;98(19):2088–2093
  26. Willson TM, Brown PJ, Sternbach DD, Henke BR. The PPARs: from orphan receptors to drug discovery. J Med Chem. 2000;43(4):527–550
  27. Berger J, Bailey P, Biswas C, Cullinan CA, Doebber TW, Hayes NS, et al. Thiazolidinediones produce a conformational change in peroxisomal proliferator-activated receptor-gamma: binding and activation correlate with antidiabetic actions in db/db mice. Endocrinology. 1996;137(10):4189–4195
  28. Lehmann JM, Lenhard JM, Oliver BB, Ringold GM, Kliewer SA. Peroxisome proliferator-activated receptors alpha and gamma are activated by indomethacin and other non-steroidal anti-inflammatory drugs. J Biol Chem. 1997;272(6):3406–3410
  29. Leibowitz MD, Fievet C, Hennuyer N, Peinado-Onsurbe J, Duez H, Bergera J, et al. Activation of PPARdelta alters lipid metabolism in db/db mice. FEBS Lett. 2000;473(3):333–336
  30. Oliver WR, Shenk JL, Snaith MR, Russell CS, Plunket KD, Bodkin NL, et al. A selective peroxisome proliferator-activated receptor delta agonist promotes reverse cholesterol transport. Proc Natl Acad Sci U S A. 2001;98(9):5306–5311
  31. Tenenbaum A, Fisman EZ, Motro M. Metabolic syndrome and type 2 diabetes mellitus: focus on peroxisome proliferator activated receptors (PPAR). Cardiovasc Diabetol. 2003;2:4
  32. Vosper H, Khoudoli GA, Graham TL, Palmer CN. Peroxisome proliferator-activated receptor agonists, hyperlipidaemia, and atherosclerosis. Pharmacol Ther. 2002;95(1):47–62Fruchart JC, Staels B, Duriez P. The role of fibric acids in atherosclerosis. Curr Atheroscler Rep. 2001;3(1):83–92
  33. Patel CB, De Lemos JA, Wyne KL, McGuire DK. Thiazolidinediones and risk for atherosclerosis: pleiotropic effects of PPar gamma agonism. Diab Vasc Dis Res. 2006;3(2):65–71
  34. Carmeliet P. Angiogenesis in health and disease. Nat Med. 2003;9(6):653–660
  35. Pugh CW, Ratcliffe PJ. Regulation of angiogenesis by hypoxia: role of the HIF system. Nat Med. 2003;9(6):677–684
  36. Buschmann I, Schaper W. The pathophysiology of the collateral circulation (arteriogenesis). J Pathol. 2000;190(3):338–342
  37. Semenza GL. Hydroxylation of HIF-1: oxygen sensing at the molecular level. Physiology (Bethesda). 2004;19:176–182
  38. Carmeliet P, Ferreira V, Breier G, Pollefeyt S, Kieckens L, Gertsenstein M, et al. Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature. 1996;380(6573):435–439
  39. Olofsson B, Pajusola K, Kaipainen A, von Euler G, Joukov V, Saksela O, et al. Vascular endothelial growth factor B, a novel growth factor for endothelial cells. Proc Natl Acad Sci U S A. 1996;93(6):2576–2581
  40. Joukov V, Pajusola K, Kaipainen A, Chilov D, Lahtinen I, Kukk E, et al. A novel vascular endothelial growth factor, VEGF-C, is a ligand for the Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases. EMBO J. 1996;15(2):290–298
  41. Stacker SA, Caesar C, Baldwin ME, Thornton GE, Williams RA, Prevo R, et al. VEGF-D promotes the metastatic spread of tumor cells via the lymphatics. Nat Med. 2001;7(2):186–191
  42. Veikkola T, Jussila L, Makinen T, Karpanen T, Jeltsch M, Petrova TV, et al. Signalling via vascular endothelial growth factor receptor-3 is sufficient for lymphangiogenesis in transgenic mice. EMBO J. 2001;20(6):1223–1231
  43. Lim HS, Lip GY, Blann AD. Angiopoietin-1 and angiopoietin-2 in diabetes mellitus: relationship to VEGF, glycaemic control, endothelial damage/dysfunction and atherosclerosis. Atherosclerosis. 2005;180(1):113–118
  44. Ferrara N. Role of vascular endothelial growth factor in regulation of physiological angiogenesis. Am J Physiol Cell Physiol. 2001;280(6):C1358–C1366
  45. Davis S, Aldrich TH, Jones PF, Acheson A, Compton DL, Jain V, et al. Isolation of angiopoietin-1, a ligand for the TIE2 receptor, by secretion-trap expression cloning. Cell. 1996;87(7):1161–1169
  46. Papapetropoulos A, Garcia-Cardena G, Dengler TJ, Maisonpierre PC, Yancopoulos GD, Sessa WC. Direct actions of angiopoietin-1 on human endothelium: evidence for network stabilization, cell survival, and interaction with other angiogenic growth factors. Lab Invest. 1999;79(2):213–223
  47. Maisonpierre PC, Suri C, Jones PF, Bartunkova S, Wiegand SJ, Radziejewski C, et al. Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science. 1997;277(5322):55–60
  48. Lobov IB, Brooks PC, Lang RA. Angiopoietin-2 displays VEGF-dependent modulation of capillary structure and endothelial cell survival in vivo. Proc Natl Acad Sci U S A. 2002;99(17):11205–11210
  49. Moulton KS. Plaque angiogenesis and atherosclerosis. Curr Atheroscler Rep. 2001;3(3):225–233
  50. Martin A, Komada MR, Sane DC. Abnormal angiogenesis in diabetes mellitus. Med Res Rev. 2003;23(2):117–145
  51. Patz A. Clinical and experimental studies on role of oxygen in retrolental fibroplasia. Trans Am Acad Ophthalmol Otolaryngol. 1954;58(1):45–50
  52. Lip PL, Belgore F, Blann AD, Hope-Ross MW, Gibson JM, Lip GY. Plasma VEGF and soluble VEGF receptor FLT-1 in proliferative retinopathy: relationship to endothelial dysfunction and laser treatment. Invest Ophthalmol Vis Sci. 2000;41(8):2115–2119
  53. Nyengaard JR, Rasch R. The impact of experimental diabetes mellitus in rats on glomerular capillary number and sizes. Diabetologia. 1993;36(3):189–194
  54. Loots MA, Lamme EN, Zeegelaar J, Mekkes JR, Bos JD, Middelkoop E. Differences in cellular infiltrate and extracellular matrix of chronic diabetic and venous ulcers versus acute wounds. J Invest Dermatol. 1998;111(5):850–857
  55. Ferguson MW, Herrick SE, Spencer MJ, Shaw JE, Boulton AJ, Sloan P. The histology of diabetic foot ulcers. Diabet Med. 1996;13(Suppl. 1):S30–S33
  56. Waltenberger J. Impaired collateral vessel development in diabetes: potential cellular mechanisms and therapeutic implications. Cardiovasc Res. 2001;49(3):554–560
  57. Barzilay JI, Kronmal RA, Bittner V, Eaker E, Evans C, Foster ED. Coronary artery disease and coronary artery bypass grafting in diabetic patients aged>or=65 years (report from the Coronary Artery Surgery Study [CASS] Registry). Am J Cardiol. 1994;74(4):334–339
  58. Yarom R, Zirkin H, Stammler G, Rose AG. Human coronary microvessels in diabetes and ischaemia. Morphometric study of autopsy material. J Pathol. 1992;166(3):265–270
  59. Rivard A, Silver M, Chen D, Kearney M, Magner M, Annex B, et al. Rescue of diabetes-related impairment of angiogenesis by intramuscular gene therapy with adeno-VEGF. Am J Pathol. 1999;154(2):355–363
  60. Cross SE, Thompson MJ, Roberts MS. Distribution of systemically administered ampicillin, benzylpenicillin, and flucloxacillin in excisional wounds in diabetic and normal rats and effects of local topical vasodilator treatment. Antimicrob Agents Chemother. 1996;40(7):1703–1710
  61. Maxfield EK, Cameron NE, Cotter MA, Dines KC. Angiotensin II receptor blockade improves nerve function, modulates nerve blood flow and stimulates endoneurial angiogenesis in streptozotocin-diabetic rats and nerve function. Diabetologia. 1993;36(12):1230–1237
  62. Stevens MJ, Obrosova I, Cao X, Van Huysen C, Greene DA. Effects of DL-alpha-lipoic acid on peripheral nerve conduction, blood flow, energy metabolism, and oxidative stress in experimental diabetic neuropathy. Diabetes. 2000;49(6):1006–1015
  63. Wideroff L, Gridley G, Mellemkjaer L, Chow WH, Linet M, Keehn S, et al. Cancer incidence in a population-based cohort of patients hospitalized with diabetes mellitus in Denmark. J Natl Cancer Inst. 1997;89(18):1360–1365
  64. Aiello LP, Avery RL, Arrigg PG, Keyt BA, Jampel HD, Shah ST, et al. Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med. 1994;331(22):1480–1487
  65. Tsuchida K, Makita Z, Yamagishi S, Atsumi T, Miyoshi H, Obara S, et al. Suppression of transforming growth factor beta and vascular endothelial growth factor in diabetic nephropathy in rats by a novel advanced glycation end product inhibitor, OPB-9195. Diabetologia. 1999;42(5):579–588
  66. Kampfer H, Pfeilschifter J, Frank S. Expressional regulation of angiopoietin-1 and -2 and the tie-1 and -2 receptor tyrosine kinases during cutaneous wound healing: a comparative study of normal and impaired repair. Lab Invest. 2001;81(3):361–373
  67. Boger RH, Bode-Boger SM, Szuba A, Tsao PS, Chan JR, Tangphao O, et al. Asymmetric dimethylarginine (ADMA): a novel risk factor for endothelial dysfunction: its role in hypercholesterolemia. Circulation. 1998;98(18):1842–1847
  68. Halvorsen YD, Bursell SE, Wilkison WO, Clermont AC, Brittis M, McGovern TJ, et al. Vasodilation of rat retinal microvessels induced by monobutyrin. Dysregulation in diabetes. J Clin Invest. 1993;92(6):2872–2876
  69. Xin X, Yang S, Kowalski J, Gerritsen ME. Peroxisome proliferator-activated receptor gamma ligands are potent inhibitors of angiogenesis in vitro and in vivo. J Biol Chem. 1999;274(13):9116–9121
  70. Panigrahy D, Singer S, Shen LQ, Butterfield CE, Freedman DA, Chen EJ, et al. PPARgamma ligands inhibit primary tumor growth and metastasis by inhibiting angiogenesis. J Clin Invest. 2002;110(7):923–932
  71. Murata T, He S, Hangai M, Ishibashi T, Xi XP, Kim S, et al. Peroxisome proliferator-activated receptor-gamma ligands inhibit choroidal neovascularization. Invest Ophthalmol Vis Sci. 2000;41(8):2309–2317
  72. Peeters LL, Vigne JL, Tee MK, Zhao D, Waite LL, Taylor RN. PPARgamma represses VEGF expression in human endometrial cells: implications for uterine angiogenesis. Angiogenesis. 2005;8(4):373–379
  73. Chu K, Lee ST, Koo JS, Jung KH, Kim EH, Sinn DI, et al. Peroxisome proliferator-activated receptor-gamma-agonist, rosiglitazone, promotes angiogenesis after focal cerebral ischemia. Brain Res. 2006;1093(1):208–218
  74. Yamakawa K, Hosoi M, Koyama H, Tanaka S, Fukumoto S, Morii H, et al. Peroxisome proliferator-activated receptor-gamma agonists increase vascular endothelial growth factor expression in human vascular smooth muscle cells. Biochem Biophys Res Commun. 2000;271(3):571–574
  75. Jozkowicz A, Dulak J, Piatkowska E, Placha W, Dembinska-Kiec A. Ligands of peroxisome proliferator-activated receptor-gamma increase the generation of vascular endothelial growth factor in vascular smooth muscle cells and in macrophages. Acta Biochim Pol. 2000;47(4):1147–1157
  76. Pistrosch F, Herbrig K, Oelschlaegel U, Richter S, Passauer J, Fischer S, et al. PPARgamma-agonist rosiglitazone increases number and migratory activity of cultured endothelial progenitor cells. Atherosclerosis. 2005;183(1):163–167
  77. Chintalgattu V, Harris GS, Akula SM, Katwa LC. PPAR-gamma agonists induce the expression of VEGF and its receptors in cultured cardiac myofibroblasts. Cardiovasc Res. 2007;74(1):140–150
  78. Liu HB, Hu YS, Medcalf RL, Simpson RW, Dear AE. Thiazolidinediones inhibit TNFalpha induction of PAI-1 independent of PPARgamma activation. Biochem Biophys Res Commun. 2005;334(1):30–37
  79. Turturro F, Oliver R, Friday E, Nissim I, Welbourne T. Troglitazone and pioglitazone interactions via PPAR-gamma-independent and -dependent pathways in regulating physiological responses in renal tubule-derived cell lines. Am J Physiol Cell Physiol. 2007;292(3):C1137–C1146
  80. Shiau CW, Yang CC, Kulp SK, Chen KF, Chen CS, Huang JW, et al. Thiazolidenediones mediate apoptosis in prostate cancer cells in part through inhibition of Bcl-xL/Bcl-2 functions independently of PPARgamma. Cancer Res. 2005;65(4):1561–1569
  81. Galli A, Ceni E, Crabb DW, Mello T, Salzano R, Grappone C, et al. Antidiabetic thiazolidinediones inhibit invasiveness of pancreatic cancer cells via PPARgamma independent mechanisms. Gut. 2004;53(11):1688–1697
  82. Gardner OS, Shiau CW, Chen CS, Graves LM. Peroxisome proliferator-activated receptor gamma-independent activation of p38 MAPK by thiazolidinediones involves calcium/calmodulin-dependent protein kinase II and protein kinase R: correlation with endoplasmic reticulum stress. J Biol Chem. 2005;280(11):10109–10118
  83. Kim EH, Na HK, Surh YJ. Upregulation of VEGF by 15-deoxy-Delta12,14-prostaglandin J2 via heme oxygenase-1 and ERK1/2 signaling in MCF-7 cells. Ann N Y Acad Sci. 2006;1090:375–384
  84. Vu-Dac N, Schoonjans K, Laine B, Fruchart JC, Auwerx J, Staels B. Negative regulation of the human apolipoprotein A-I promoter by fibrates can be attenuated by the interaction of the peroxisome proliferator-activated receptor with its response element. J Biol Chem. 1994;269(49):31012–31018
  85. Scatena R, Bottoni P, Vincenzoni F, Messana I, Martorana GE, Nocca G, et al. Bezafibrate induces a mitochondrial derangement in human cell lines: a PPAR-independent mechanism for a peroxisome proliferator. Chem Res Toxicol. 2003;16(11):1440–1447
  86. Selim E, Frkanec JT, Cunard R. Fibrates upregulate TRB3 in lymphocytes independent of PPAR alpha by augmenting CCAAT/enhancer-binding protein beta (C/EBP beta) expression. Mol Immunol. 2007;44(6):1218–1229
  87. Zhang X, Tanaka N, Nakajima T, Kamijo Y, Gonzalez FJ, Aoyama T. Peroxisome proliferator-activated receptor alpha-independent peroxisome proliferation. Biochem Biophys Res Commun. 2006;346(4):1307–1311
  88. Wang D, Wang H, Guo Y, Ning W, Katkuri S, Wahli W, et al. Crosstalk between peroxisome proliferator-activated receptor delta and VEGF stimulates cancer progression. Proc Natl Acad Sci U S A. 2006;103(50):19069–19074
  89. Marin HE, Peraza MA, Billin AN, Willson TM, Ward JM, Kennett MJ, et al. Ligand activation of peroxisome proliferator-activated receptor beta inhibits colon carcinogenesis. Cancer Res. 2006;66(8):4394–4401
  90. Biscetti F, Gaetani E, Flex A, Aprahamian T, Hopkins T, Straface G, et al. Selective activation of peroxisome proliferator-activated receptor (PPAR)alpha and PPAR gamma induces neoangiogenesis through a vascular endothelial growth factor-dependent mechanism. Diabetes. 2008;57(5):1394–1404
  91. Piqueras L, Reynolds AR, Hodivala-Dilke KM, Alfranca A, Redondo JM, Hatae T, et al. Activation of PPARbeta/delta induces endothelial cell proliferation and angiogenesis. Arterioscler Thromb Vasc Biol. 2007;27(1):63–69
  92. Balakumar P, Rose M, Ganti SS, Krishan P, Singh M. PPAR dual agonists: are they opening Pandora's Box?. Pharmacol Res. 2007;56(2):91–98
  93. Hellmold H, Zhang H, Andersson U, Blomgren B, Holland T, Berg AL, et al. Tesaglitazar, a PPARalpha/gamma agonist, induces interstitial mesenchymal cell DNA synthesis and fibrosarcomas in subcutaneous tissues in rats. Toxicol Sci. 2007;98(1):63–74
  94. Kendall DM, Rubin CJ, Mohideen P, Ledeine JM, Belder R, Gross J, et al. Improvement of glycemic control, triglycerides, and HDL cholesterol levels with muraglitazar, a dual (alpha/gamma) peroxisome proliferator-activated receptor activator, in patients with type 2 diabetes inadequately controlled with metformin monotherapy: A double-blind, randomized, pioglitazone-comparative study. Diabetes Care. 2006;29(5):1016–1023
  95. Mittra S, Sangle G, Tandon R, Sharma S, Roy S, Khanna V, et al. Increase in weight induced by muraglitazar, a dual PPARalpha/gamma agonist, in db/db mice: adipogenesis/or oedema?. Br J Pharmacol. 2007;150(4):480–487
  96. Pistrosch F, Passauer J, Fischer S, Fuecker K, Hanefeld M, Gross P. In type 2 diabetes, rosiglitazone therapy for insulin resistance ameliorates endothelial dysfunction independent of glucose control. Diabetes Care. 2004;27(2):484–490
  97. Senger DR, Van de Water L, Brown LF, Nagy JA, Yeo KT, Yeo TK, et al. Vascular permeability factor (VPF, VEGF) in tumor biology. Cancer Metastasis Rev. 1993;12(3–4):303–324
  98. Khurana R, Simons M, Martin JF, Zachary IC. Role of angiogenesis in cardiovascular disease: a critical appraisal. Circulation. 2005;112(12):1813–1824
  99. Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med. 2007;356(24):2457–2471
  100. Jackson TC, Mi Z, Bastacky SI, McHale T, Melhem MF, Sonalker PA, et al. PPAR alpha agonists improve renal preservation in kidneys subjected to chronic in vitro perfusion: interaction with mannitol. Transpl Int. 2007;20(3):277–290
  101. Skrha J, Stulc T, Hilgertova J, Weiserova H, Kvasnicka J, Ceska R. Effect of simvastatin and fenofibrate on endothelium in Type 2 diabetes. Eur J Pharmacol. 2004;493(1–3):183–189

PII: S0939-4753(09)00104-5

doi: 10.1016/j.numecd.2009.04.011

Nutrition, Metabolism & Cardiovascular Diseases
Volume 19, Issue 11 , Pages 751-759 , December 2009