Effect of Rosiglitazone on Coronary Angiogenesis in Diabetic and Control Rats

Document Type : Original Article (s)

Authors

1 MSc Student, Student Research Committee, Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

2 Associate Professor, Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

3 Assistant Professor, Department of Anatomy, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

4 Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

Abstract

Background: Peroxisome proliferator–activated receptors (PPARs) are ligand-activated transcription factors of nuclear receptor superfamily, consisting of three subtypes: PPARα, γ, β/δ. Clinical evidence suggests that PPARs may be involved in regulating angiogenesis. In this study, we examined the hypothesis that whether activation of PPARγ by Rosiglitazone, a PPARγ agonist, can alter coronary angiogenesis in diabetic and control rats.Methods: Twenty four male rats were randomly divided into four groups as follows: group 1: control rats received vehicle; group 2: control rats received Rosiglitazone (8mg/kg/day) by gavage every day; group 3: diabetic rats received vehicle; group 4: diabetic rats received Rosiglitazone (8mg/kg/day) by gavage everyday. All rats were sacrified after 21 days and their hearts muscles were harvested for immonohistochemistry.Finding: The mean capillary density in control rats was higher than diabetic rats (P = 0.08). Rosiglitazone treatment could not change capillary density of the heart in diabetic rats (121.71 ± 13.32 versus 136.62 ± 7.02/mm2) and nondiabetic rats (153.78 ± 11.08 versus 135.96 ± 4.3/mm2).Conclusion: Our findings demonstrate that diabetes is associated with reduced capillary density in the heart and PPARγ activation by Rosiglitazone could not alter angiogenesis in diabetic and non-diabetic rats.

Keywords

References

  1. Kersten S, Desvergne B, Wahli W. Roles of PPARs in health and disease. Nature 2000; 405(6785): 421-4.
  2. Issemann I, Green S. Activation of a member of the steroid hormone receptor superfamily by pe-roxisome proliferators. Nature 1990; 347(6294): 645-50.
  3. Pozzi A, Capdevila JH. PPARalpha Ligands as Antitumorigenic and Antiangiogenic Agents. PPAR Res 2008; 2008: 906542.
  4. 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): 18779-89.
  5. Delerive P, Martin-Nizard F, Chinetti G, Trottein F, Fruchart JC, Najib J, et al. Peroxisome prolif-erator-activated receptor activators inhibit thrombin-induced endothelin-1 production in human vascular endothelial cells by inhibiting the activator protein-1 signaling pathway. Circ Res 1999; 85(5): 394-402.
  6. Shearer BG, Hoekstra WJ. Peroxisome prolifera-tor-Activated receptors (PPARs): Choreogra-phers of Metabolic Gene Transcription. Cell transmissions 2002; 18(3): 3-10
  7. Lazar MA. PPAR gamma, 10 years later. Bio-chimie 2005; 87(1): 9-13.
  8. Blaschke F, Takata Y, Caglayan E, Law RE, Hsueh WA. Obesity, peroxisome proliferator-activated receptor, and atherosclerosis in type 2 diabetes. Arterioscler Thromb Vasc Biol 2006; 26(1): 28-40.
  9. Wang CH, Ciliberti N, Li SH, Szmitko PE, Weisel RD, Fedak PW, et al. Rosiglitazone facilitates angiogenic progenitor cell differentiation toward endothelial lineage: a new paradigm in glitazone pleiotropy. Circulation 2004; 109(11): 1392-400.
  10. Panigrahy D, Singer S, Shen LQ, Butterfield CE, Freedman DA, Chen EJ, et al. PPARgamma lig-ands inhibit primary tumor growth and metasta-sis by inhibiting angiogenesis. J Clin Invest 2002; 110(7): 923-32.
  11. Peeters LL, Vigne JL, Tee MK, Zhao D, Waite LL, Taylor RN. PPAR gamma represses VEGF expression in human endometrial cells: implica-tions for uterine angiogenesis. Angiogenesis 2005; 8(4): 373-9.
  12. Boodhwani M, Sodha NR, Mieno S, Xu SH, Feng J, Ramlawi B, et al. Functional, cellular, and molecular characterization of the angiogen-ic response to chronic myocardial ischemia in diabetes. Circulation 2007; 116(11 Suppl): I31-I37.
  13. Kivela R, Silvennoinen M, Lehti M, Jalava S, Vihko V, Kainulainen H. Exercise-induced ex-pression of angiogenic growth factors in skeletal muscle and in capillaries of healthy and diabetic mice. Cardiovasc Diabetol 2008; 7: 13.
  14. 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): 355-63.
  15. . Jacobi J, Porst M, Cordasic N, Namer B, Schmieder RE, Eckardt KU, et al. Subtotal ne-phrectomy impairs ischemia-induced angiogene-sis and hindlimb re-perfusion in rats. Kidney Int 2006; 69(11): 2013-21.
  16. Abaci A, Oguzhan A, Kahraman S, Eryol NK, Unal S, Arinc H, et al. Effect of diabetes mellitus on formation of coronary collateral vessels. Cir-culation 1999; 99(17): 2239-42.
  17. Chou E, Suzuma I, Way KJ, Opland D, Clermont AC, Naruse K, et al. Decreased cardiac expres-sion of vascular endothelial growth factor and its receptors in insulin-resistant and diabetic States: a possible explanation for impaired collateral formation in cardiac tissue. Circulation 2002 Jan 22; 105(3): 373-9.
  18. Khazaei M. Effects of diabetes on myocardial capillary density and serum biomarkers of angi-ogenesis in male rats. Journal of Isfahan Medi-cal School 2011; 29(132): 1-14
  19. Waltenberger J, Lange J, Kranz A. Vascular en-dothelial growth factor-A-induced chemotaxis of monocytes is attenuated in patients with diabe-tes mellitus: A potential predictor for the individ-ual capacity to develop collaterals. Circulation 2000; 102(2): 185-90.
  20. Waltenberger J. Impaired collateral vessel devel-opment in diabetes: potential cellular mecha-nisms and therapeutic implications. Cardiovasc Res 2001; 49(3): 554-60.
  21. Sasso FC, Torella D, Carbonara O, Ellison GM, Torella M, Scardone M, et al. Increased vascular endothelial growth factor expression but im-paired vascular endothelial growth factor recep-tor signaling in the myocardium of type 2 diabet-ic patients with chronic coronary heart disease. J Am Coll Cardiol 2005; 46(5): 827-34.
  22. Balakumar P, Rose M, Ganti SS, Krishan P, Singh M. PPAR dual agonists: are they opening Pandora's Box? Pharmacol Res 2007; 56(2): 91-8.
  23. Martens FM, Rabelink TJ, Op't RJ, de Koning EJ, Visseren FL. TNF-alpha induces endothelial dys-function in diabetic adults, an effect reversible by the PPAR-gamma agonist pioglitazone. Eur Heart J 2006; 27(13): 1605-9.
  24. Natali A, Baldeweg S, Toschi E, Capaldo B, Barbaro D, Gastaldelli A, et al. Vascular effects of improving metabolic control with metformin or rosiglitazone in type 2 diabetes. Diabetes Care 2004; 27(6): 1349-57.
  25. Murata T, He S, Hangai M, Ishibashi T, Xi XP, Kim S, et al. Peroxisome proliferator-activated receptor-gamma ligands inhibit choroidal neo-vascularization. Invest Ophthalmol Vis Sci 2000; 41(8): 2309-17.
  26. Huang PH, Sata M, Nishimatsu H, Sumi M, Hirata Y, Nagai R. Pioglitazone ameliorates en-dothelial dysfunction and restores ischemia-induced angiogenesis in diabetic mice. Biomed Pharmacother 2008; 62(1): 46-52.
  27. Chu K, Lee ST, Koo JS, Jung KH, Kim EH, Sinn DI, et al. Peroxisome proliferator-activated re-ceptor-gamma-agonist, rosiglitazone, promotes angiogenesis after focal cerebral ischemia. Brain Res 2006; 1093(1): 208-18.
  28. 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): 163-7.
Journal of Isfahan Medical School
Volume 29, Issue 134 - Serial Number 134
March and April 2011
Pages 386-393

Files

History

  • Receive Date: 11 May 2011
  • Revise Date: 26 May 2024
  • Accept Date: 06 April 2022

Share

How to cite

Statistics