Objective:To evaluate whether the berberine treatment can improve endothelial repair capacity of early endothelial progenitor cells (EPCs) from prehypertensive subjects through increasing CXC chemokine receptor 4 (CXCR4) signaling.Methods:EPCs were isolated from prehypertensive and healthy subjects and cultured.in vivo reendothelialization capacity of EPCs from prehypertensive patients with or without in vitro berberine treatment was examined in a nude mouse model of carotid artery injury.The protein expressions of CXCR4/Janus kinase-2 (JAK-2) signaling of in vitro EPCs were detected by Westem blot analysis.Results:CXCR4 signaling and alteration in migration and adhesion functions of EPCs were evaluated.Basal CXCR4 expression was significantly reduced in EPCs from prehypertensive patients compared with normal subjects (P＜0.01).Also,the phosphorylation of JAK-2 of EPCs,a CXCR4 downstream signaling,was significantly decreased (P＜0.01).Berberine promoted CXCR4/JAK-2 signaling expression of in vitro EPCs (P＜0.01).Transplantation of EPCs pretreated with berberine markedly accelerated in vivo reendothelialization (P＜0.01).The increased in vitro function and in vivo reendothelialization capacity of EPCs were inhibited by CXCR4 neutralizing antibody or pretreatment with JAK-2 inhibitor AG490,respectively (P＜0.01).Conclusion:Berberinemodified EPCs via up-regulation of CXCR4 signaling contributes to enhanced endothelial repair capacity in prehypertension,indicating that berberine may be used as a novel potential primary prevention means against prehypertension-related atherosclerotic cardiovascular disease.