Berberine-Promoted CXCR4 Expression Accelerates Endothelial Repair Capacity of Early Endothelial Progenitor Cells in Persons with Prehypertension  

作　　者：SHAO Yi-jia TAO Jun YU Bing-bo MENG Dan YANG Xu-long SUN Jia-pan QIU Yan-xia ZHANG Xiao-yu 

机构地区：[1]Department of Hypertension and Vascular Disease,the First Affiliated Hospital of Sun Yat-Sen University,Key Laboratory on Assisted Circulation,Ministry of Health,Guangzhou 510080,China

出　　处：《Chinese Journal of Integrative Medicine》2018年第12期897-904,共8页中国结合医学杂志（英文版）

基　　金：Supported by the grants from the National Natural Science Foundation of China(No.81500205,No.31530023);the Nature Science Foundation of Guangdong(No.2016A030310184)

摘　　要：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 Western 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： Berberine- modified 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.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 Western 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： Berberine- modified 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.

关 键 词：PREHYPERTENSION BERBERINE endothelial progenitor cells REENDOTHELIALIZATION CXC chemokine receptor 4 

分 类 号：R544.1[医药卫生—心血管疾病]