The Effect of Atorvastatin on the Viability of Ischemic Skin Flaps in Diabetic Rats.

Abstract

Endothelial progenitor cells play a critical role in neovascularization. However, the mobilization, recruitment, and functional capacity of endothelial progenitor cells are significantly impaired in diabetes. Statins have been shown to augment the number and improve the function of endothelial progenitor cells. This study investigated the effects of statins on the viability of ischemic skin flaps in diabetic rats. Twenty normal and 40 diabetic Sprague-Dawley rats were included in this study. Atorvastatin (10 mg/kg/day) was administered orally in 20 diabetic rats at 2 weeks before flap surgery for 21 consecutive days. Other rats received equal vehicle. Two weeks after first gavage, a 3 × 10-cm skin flap was established on the backs of rats. The necrotic area of each skin flap was measured at 7 days postoperatively. Capillary density and endothelial progenitor cells recruited to the flaps were analyzed using immunofluorescence staining. Circulating endothelial progenitor cell number was determined by flow cytometry. In vitro migration and tube formation experiments were used to analyze the function of endothelial progenitor cells. Atorvastatin treatment increased flap survival rate and capillary density. In addition, more endothelial progenitor cells were identified in peripheral blood and skin flaps in diabetic rats receiving atorvastatin. Atorvastatin treatment also restored the impaired function of diabetic endothelial progenitor cells in migration and tube formation. Atorvastatin notably promoted neovascularization and enhanced the viability of ischemic skin flaps in diabetic rats, which may be mediated at least partially by augmenting the number and restoring the functional capacity of endothelial progenitor cells.