title: Lacidipine improves endothelial repair capacity of endothelial progenitor cells from patients with essential hypertension.
abstract: BACKGROUND
  Endothelial progenitor cells (EPCs) play a critical role in maintaining the integrity of vascular endothelium following arterial injury. Lacidipine has a beneficial effect on endothelium of hypertensive patients, but limited data are available on EPCs-mediated endothelial protection. This study tests the hypothesis that lacidipine treatment can improve endothelial repair capacity of EPCs from hypertensive patients through increasing CXC chemokine receptor four (CXCR4) signaling.
  
  
  METHODS
  In vivo reendothelialization capacity of EPCs from hypertensive patients with or without in vitro lacidipine treatment was examined in a nude mouse model of carotid artery injury. Expression of CXCR4 and alteration in migration and adhesion functions of EPCs were evaluated.
  
  
  RESULTS
  Basal CXCR4 expression was markedly reduced in EPCs from hypertensive patients compared with normal subjects. In parallel, the phosphorylation of Janus kinase-2 (JAK-2) of EPCs, a CXCR4 downstream signaling, was also significantly decreased. Lacidipine promoted CXCR4/JAK-2 signaling expression of in vitro EPCs. Transplantation of EPCs pretreated with lacidipine significantly accelerated in vivo reendothelialization. The enhanced in vitro function and in vivo reendothelialization capacity of EPCs were inhibited by shRNA-mediated knockdown of CXCR4 expression or pretreatment with JAK-2 inhibitor AG490, respectively. In hypertensive patients, lacidipine treatment for 4 weeks also resulted in an upregulation of CXCR4/JAK-2 signaling of EPCs, which was associated with augmented EPCs-mediated reendothelialization and improved endothelial function.
  
  
  CONCLUSIONS
  Deterioration of CXCR4 signaling may lead to impaired EPCs-mediated reendothelialization of hypertensive patients. Lacidipine-modified EPCs via a partially CXCR4 signaling contribute to enhanced endothelial repair capacity in hypertension.
authors: Department of Hypertension and Vascular Disease, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China; Department of Cardiovascular Disease, The Jiangmen Central Hospital, Jiangmen 529030, China.
authors: Xing
authors: X
authors: Liu
authors: Gao-Xing
authors: GX
authors: Zhang
authors: Xiao-Yu
authors: XY
authors: Zhang
authors: Wen-Hao
authors: WH
authors: Xia
authors: Zhen
authors: Z
authors: Yang
authors: Chen
authors: C
authors: Su
authors: Yan-Xia
authors: YX
authors: Qiu
authors: Shi-Yue
authors: SY
authors: Xu
authors: Hong
authors: H
authors: Zhan
authors: Jun
authors: J
authors: Tao
mesh_terms: D000328:Adult; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002478:Cells, Cultured; D004095:Dihydropyridines / Q000494:pharmacology / Q000627:therapeutic use*; D042783:Endothelial Cells / Q000187:drug effects* / Q000473:pathology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology; D000075222:Essential Hypertension; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D013234:Stem Cells / Q000187:drug effects* / Q000473:pathology
chemical_list: D000959:Antihypertensive Agents; D004095:Dihydropyridines; C060285:lacidipine
keywords: Endothelial progenitor cells; Endothelium; Hypertension; Lacidipine; Reendothelialization