BACKGROUND: The aim of this study was to test the hypothesis that angiotensin converting enzyme inhibition or angiotensin II antagonism can counteract cardiac human vascular endothelial growth factor-A165 (phVEGF-A165) induced angiogenesis. METHODS: Mice were given a single intramyocardial injection of phVEGF-A165. Either enalapril or candesartan was given subcutaneously for 10 consecutive days. Hearts were harvested and capillary count was performed by immunohistochemistry. With similar design, groups of mice were sacrificed after 24 h for the determination of tissue expression of phVEGF-A protein, mRNA expression of mouse VEGF-A, and VEGF receptors 1 and 2, after pEGFP-Luc transfection for luciferase expression. RESULTS: Increased myocardial capillary density (P < .02) induced by phVEGF-A165 was counteracted by both enalapril (P < .07) and candesartan (P < .02) and then did not differ from control values. We found that phVEGF-A165 induced myocardial hVEGF-A expression (110 +/- 15 pg/heart, P < .0001). Both enalapril and candesartan decreased (P < .01) expression of hVEGF-A to a level not different from control values. Although phVEGF-A165 upregulated (P < .0001) mVEGFR-2, addition of candesartan downregulated endogenous mVEGF-A (P < .0001) and mVEGFR-2 (P < .0001) below the level in normal myocardium. Enalapril or candesartan did not effect luciferase expression. CONCLUSIONS: Enalapril and candesartan both specifically inhibit phVEGF-A165 induced myocardial angiogenesis in the normal heart. The mechanism of inhibition is a combination of inhibition of cardiac hVEGF-A expression and of decreased endogenous expression of the mVEGF ligand and receptor system.
BACKGROUND: The aim of this study was to test the hypothesis that angiotensin converting enzyme inhibition or angiotensin II antagonism can counteract cardiac humanvascular endothelial growth factor-A165 (phVEGF-A165) induced angiogenesis. METHODS:Mice were given a single intramyocardial injection of phVEGF-A165. Either enalapril or candesartan was given subcutaneously for 10 consecutive days. Hearts were harvested and capillary count was performed by immunohistochemistry. With similar design, groups of mice were sacrificed after 24 h for the determination of tissue expression of phVEGF-A protein, mRNA expression of mouseVEGF-A, and VEGF receptors 1 and 2, after pEGFP-Luc transfection for luciferase expression. RESULTS: Increased myocardial capillary density (P < .02) induced by phVEGF-A165 was counteracted by both enalapril (P < .07) and candesartan (P < .02) and then did not differ from control values. We found that phVEGF-A165 induced myocardial hVEGF-A expression (110 +/- 15 pg/heart, P < .0001). Both enalapril and candesartan decreased (P < .01) expression of hVEGF-A to a level not different from control values. Although phVEGF-A165 upregulated (P < .0001) mVEGFR-2, addition of candesartan downregulated endogenous mVEGF-A (P < .0001) and mVEGFR-2 (P < .0001) below the level in normal myocardium. Enalapril or candesartan did not effect luciferase expression. CONCLUSIONS:Enalapril and candesartan both specifically inhibit phVEGF-A165 induced myocardial angiogenesis in the normal heart. The mechanism of inhibition is a combination of inhibition of cardiac hVEGF-A expression and of decreased endogenous expression of the mVEGF ligand and receptor system.
Authors: Mohsin Hamid; Ali Ghani; Ida Micaily; Usman Sarwar; Bilal Lashari; Faizan Malik Journal: J Community Hosp Intern Med Perspect Date: 2018-06-12