Stimulatory Effect of Erythropoietin on Endothelial Repair After Vascular Injury

Abstract

Erythropoietin (EPO) fosters tissue oxygenation by stimulating erythropoiesis. More recently, EPO is recognized as a tissue protective cytokine. In this study, we tested the hypothesis that EPO promotes recovery of injured vascular endothelium. A murine model of wire-induced injury of common carotid artery was used to examine the therapeutic effect of EPO. Recombinant human EPO (1000 U/kg, s.c., biweekly) was administered for 2 weeks after which vascular reactivity of isolated carotid arteries was studied in vitro under pressurized condition using a video dimension analyzer. Changes in vascular structure were histologically assessed. Injured arteries exhibited impairment in endothelium-dependent relaxations to acetylcholine and increased thickness of the medial cross sectional area (P<0.05; n=5–7). EPO normalized the vasorelaxant response of injured arteries to acetylcholine and prevented the increase in medial cross sectional area (30±1 x 10-3 mm2; P<0.05 vs. without EPO: 37±3 x 10-3 mm2; n=6). The number of circulating endothelial progenitor cells (EPCs), defined as CD34+/Flk-1+ cells in the peripheral blood, was significantly reduced 2 weeks after vascular injury (0.016±0.005%; P<0.05 vs. non-injured control: 0.09±0.01%), but this was entirely restored by EPO (0.212±0.08%; P<0.05; n=5). Our results indicate that EPO accelerates recovery of the injured carotid artery endothelium, and such salutary effects of EPO may reflect augmentation in circulating EPCs induced by EPO.