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Abstract

EFFECT OF ISCHEMIA REPERFUSION INJURY AND ISCHEMIA PRECONDITIONING ON ANGIOGENIC RESPONSIVENESS OF CORONARY ENDOTHELIAL CELLS IN NORMAL AND STREPTOZOTOCIN (STZ) INDUCED DIABETIC RATS

Kiranj K. Chaudagar, Anita A. Mehta*

ABSTRACT

The VEGF/KDR/eNOS/NO axis in endothelial cells plays a key signalling role in prevention of heart failure but there is lack of reports on modulation of this axis by diabetes, ischemia reperfusion injury and ischemia preconditioning. Our objective was to study effect of ischemia reperfusion injury and ischemia preconditioning on angiogenic responsiveness of coronary endothelial cells (cEC) of normal and diabetic rats. Male wistar rats were divided into three groups; normal rats, diabetic rats 30ds. (30 days after administration of STZ), diabetic rats 60ds. (60 days after administration of STZ), Each group was further divided into three subgroups, sham rat hearts, ischemia-reperfused and ischemia preconditioned rat hearts. After isolation of cEC from each subgroup, angiogenic responsiveness and nitric oxide (NO) releasing properties were studied using CAM assay and griess method, respectively. An angiogenic responsiveness of cEC of normal rats significantly increased in presence of VEGF. This was suppressed by l-NAME, wortmannin, chelerythrine, ischemia reperfusion injury and diabetes. Ischemia preconditioning significantly increased VEGF induced and angiogenic responsiveness of cEC of normal and early phase diabetic rats but VEGF indepdendent angiogenic responsiveness were found only in normal rats. These effects of ischemia preconditioning were attenuated by l-NAME, wortmannin, chelerythrine. Thus, angiogenic responsiveness of cEC of normals rats is dependent on activation of VEGF/KDR/PKC+PI3K/eNOS/NO axis. An activity of this axis is increased by ischemia preconditioning whereas abolished by ischemia reperfusion injury and diabetes.

Keywords: Vascular Endothelial Growth Factor (VEGF), angiogenic responsiveness, coronary endothelial cells, diabetes, ischemia reperfusion injury, ischemia preconditioning.


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