Impairment of human cell-based vasculogenesis in rats by hypercholesterolemia-induced endothelial dysfunction and rescue with L-arginine supplementation.
Abstract
Clinical efficacy of cardiac cell therapy may be compromised by its target population, patients with endothelial dysfunction. In vivo inhibition by endothelial dysfunction has been demonstrated for protein angiogenesis but remains unclear for cell therapy. We examined whether hypercholesterolemia inhibits vasculogenic effects of transplanted human circulating progenitor cells in ischemic tissue and whether L-arginine, a nitric oxide donor, might prevent impairment. Athymic rats were fed either normal (group A) or high-cholesterol diets, the latter without (group B) or with (group C) oral L-arginine supplementation. Two weeks later, these rats underwent left femoral artery ligation followed by injection of 2 x 10(6) human circulating progenitor cells into left hind-limb muscle. A fourth group (group D) received supplemented high-cholesterol diets but no cells. Group B had biochemical evidence of endothelial dysfunction and reduced tissue endothelial nitric oxide synthase expression, whereas group A levels were the same as in group C. By 21 postoperative days, left hind-limb perfusion had recovered fully in groups A and C, partially in D, and not at all in B (38% lower than group A, P < or = .004). Lower arteriolar densities were...Continue Reading
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Induction of vascular progenitor cells from endothelial cells stimulates coronary collateral growth.
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