Modulation of PPAR-γ by telmisartan protects the heart against myocardial infarction in experimental diabetes

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• 作者：Sameer Goyal ; Sachin Arora ; Tarun Kumar Bhatt ; Prasenjit Das ; Amit Sharma ; Santosh Kumari ; Dharamvir Singh Arya
• 关键词：Myocardial infarction ; Diabetes ; Oxidative stress ; Apoptosis ; GW9662
• 刊名：Chemico-Biological Interactions
• 出版年：2010
• 出版时间：14 May 2010
• 年：2010
• 卷：185
• 期：3
• 页码：271-280
• 全文大小：2121 K

文摘

Telmisartan, an angiotensin II-receptor blocker (ARB), is a partial agonist of the peroxisome proliferator-activated receptor-gamma (PPAR-γ). We investigated whether telmisartan improved the pathophysiology of myocardial infarction in diabetes partially through the PPAR-γ pathway by assessing a variety of indices, e.g., hemodynamic, biochemical, histoarchitectural changes, and apoptosis. Diabetes was induced by a single dose of streptozotocin (70 mg/kg, IP). Diabetic rats received either telmisartan (10 mg/kg/day, orally), the PPAR-γ antagonist GW9662 (1 mg/kg/day, IP), or both for 14 days with concurrent administration of isoproterenol (85 mg/kg, SC) on days 13 and 14. Compared with diabetic controls, diabetic rats with myocardial infarction exhibited altered hemodynamic profiles and reduction in the activities of creatine kinase-MB isoenzyme, lactate dehydrogenase, superoxide dismutase, catalase, and glutathione level along with increased level of malondialdehyde in the heart. Further, diabetic animals with myocardial infarction exhibited increased myonecrosis, edema, and apoptotic cell death. Treatment with telmisartan significantly improved the redox status of the myocardium with subsequent cardiac functional recovery. However, significant effects were lowered in animals treated with telmisartan plus GW9662. Telmisartan markedly inhibited Bax expression, TUNEL-positive cells, myonecrosis, and edema. On the other hand, administration of telmisartan plus GW9662 did not elicit the same effects, nor did they increase Bcl-2 protein expression in isoproterenol-induced myocardially infarcted diabetic rats when administered concomitantly or individually. Moreover, down-regulated PPAR-γ expression in myocardially infarcted diabetic hearts was increased by telmisartan treatment. In addition to class effects of ARBs, telmisartan reduces oxidative stress and apoptosis and improves cardiac function via the PPAR-γ pathway.