Tissue Inhibition of Angiotensin-Converting Enzyme Activity Stimulates Angiogenesis In Vivo

• DOI: 10.1161/01.cir.99.23.3043
• Publication Date: 2012-06-12T00:42:29Z
• Authors: Jean-Etienne Fabre; Alain Rivard; Meredith Magner; Marcy Silver; Jeffrey M. Isner
• Keywords: Captopril; Therapeutic angiogenesis

Background —Endothelial cells (ECs) represent the critical cellular element responsible for postnatal angiogenesis. Because ACE inhibitors may favorably affect endothelial function, we investigated hypothesis that administration of inhibitor quinaprilat could enhance angiogenesis in vivo. Methods and Results —Ten days after resection 1 femoral artery, New Zealand White (NZW) rabbits were randomly assigned to receive recombinant human vascular growth factor (rhVEGF) administered as a single intra-arterial injection (n=6), (n=8) or captopril (n=7) daily subcutaneous injection, no treatment (controls, n=6). Angiogenesis was monitored vivo by measurement blood pressure, vasoreactivity, resistance ischemic versus normal limbs at day 10 (D10) D40; angiographic studies identify sites neovascularization performed D10 D40, morphometric analysis capillary density limb necropsy (D40). Both functional morphological outcomes documented augmented quinaprilat-treated similar observed rhVEGF superior with either drug (controls). Residual activity equivalent groups plasma (42.54±0.03% 41.53±0.02%, P =NS) but not tissue, where lowered significantly ( <0.01) compared (13% 61%). Conclusions —ACE inhibition promotes rabbit model hindlimb ischemia. Thus, nonsulfhydryl high tissue affinity be potentially useful therapeutic tissues. Moreover, previous evidence benefits patients myocardial ischemia due part collateral development.