1012-103 Restoration of Endothelial Function in Hypercholesterolemic Rabbit by Intermittent Administration of Vascular Endothelial Growth Factor

Endothelial dysfunction in hypercholesterolemia causes abnormal arterial vasoreactivity and precedes the onset of atherosclerosis, Vascular endothelial growth factor (VEGF) is an endothelial cell (EC) specific mitogen that has been shown to stimulate EC proliferation in vitro and in vivo. We investigated the hypothesis that VEGF could also modulate EC dysfunction and thereby improve endothelium-dependent vasoreactivity, impaired due to hypercholesterolemia. Hypercholesterolemic rabbits fed a 1% cholesterol diet for 6 weeks were treated with intravenous administration of 300μg VEGF (VEGF group; n=8) or 0.9% saline solution (control group; n=9) twice a week for 3 weeks, during which time both groups continued to receive cholesterol diet. All rabbits were evaluated by in vivo vasomotion study; 8 normal (non-cholesterol and non-treated) rabbits were evaluated as well. The vasoreactive response to acetylcholine, serotonin and nitroprusside were calculated from flow velocity measured by Doppler wire, vessel diameter obtained from angiograms, and intra-arterial blood pressure recorded at the proximal external iliac artery. The resistance response to endotheliumdependent and -independent agonists recovered in VEGF group, as illustrated below. Furthermore, average intimal thickness of external iliac artery and lower abdominal aorta in VEGF group was significantly less than control group (VEGF=0.010±0.008 vs control=0,106±0.036, P<0,05).ConclusionIntermittent systemic administration of VEGF improves endothelial dysfunction and attenuates intimal thickness in hypercholesterolemic rabbit