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低氧诱导因子修饰内皮祖细胞促血管新生的研究 (PDF)

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2007年第5期
页码:
497-510
栏目:
基础研究
出版日期:
2007-10-01

文章信息/Info

Title:
Angiogenesis by hypoxia inducible factor1α transfected endothelial progenitor cells
作者:
姜萌;  王彬尧;  王长谦;  何奔; 范华骅;  邵琴;  黄定九
上海交通大学医学院附属仁济医院心内科， 上海 200001
Author(s):
JIANG Meng;  WANG Binyao;  WANG Changqian;  HE Ben;  FAN Huahua;  SHAO Qin;  HUANG Dingjiu
Department of Cardiology, Renji Hospital, Shanghai Jiaotong University,College of Medicine, Shanghai 200001, China
关键词:
低氧诱导因子1α; 内皮祖细胞; 缺血;  血管新生; 低氧
Keywords:
hypoxia inducible factor1α;  endothelial progenitor cells;  ischemia;  angiogenesis;  hypoxia
分类号:
R322.1
DOI:
-
文献标识码:
A
摘要:
目的 观察低氧诱导因子（hypoxia inducible factor1α, HIF1α）转染内皮祖细胞（endothelial progenitor cells, EPCs）后，EPCs在体外的扩增及迁移功能改变及对体内缺血下肢血管新生的影响。方法 在人外周血EPCs中导入人HIF1α基因。 结果 转染后的EPCs中HIF1α、血管内皮生长因子(vascular endothelial growth factor, VEGF)mRNA及蛋白表达升高，并被特异性siRNAHIF1α 中度抑制; 功能学检测示HIF1α过表达增加了EPC在体外的分化、扩增、迁移；内皮细胞(EC)标记物CD31、VEGFR2、eNOS及VEGF、NO分泌增加；移植HIF1αEPCs至缺血下肢后可见外源性EPCs存在于缺血部位； HIF1αEPCs较对照组进一步促进体内毛细血管数目增加。结论 在体外，HIF1α转染后的EPCs扩增及迁移功能改善；在体内，可促进缺血下肢的局部血管新生。
Abstract:
AIM To observe the ex vivo cell proliferation and migration and in vivo angiogenesis from hindlimb ischemia, hypoxia inducible factor1α(HIF1α) was introduced to endothelial progenitor cells (EPCs). METHODS To address this issue, human endothelial progenitor cells were electroporated with human HIF1α vector in vitro. RESULTS HIF1α mRNA and protein expressions were increased after HIF1αtransfection. This was accompanied by VEGF mRNA induction and increased VEGF secretion. Hypoxiastimulated VEGF mRNA induction was moderately abrogated by HIF1αspecific siRNA. Functional studies showed that HIF1α overexpression further promoted hypoxiainduced EPCs differentiation, proliferation and migration. The expressions of endothelial cell markers CD31, VEGFR2 (FLK1) and eNOS as well as VEGF and NO secretions were also increased. Furthermore, in an in vivo model of hindlimb ischemia, HIF1αtransfected EPCs had clearly homed to ischemia. A higher revascularization potential was also evidenced by increased capillary density at the injury site. CONCLUSION In vitro, HIF1α modified EPCs enhances EPCs proliferation and migration. In vivo, genemodified EPCs facilitate the strategy of cell transplantation to augment naturally impaired neovascularization in an animal model of experimentally induced limb ischemia.

参考文献/References

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［4］ 姜萌，王长谦， 王彬尧, 等. 低氧诱导因子过表达对人外周血内皮祖细胞分化影响的体外研究 ［J］. 中国实验血液学杂志， 2006, 14（3）：565-570.

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［10］Ferrari N, Glod J, Lee J, et al. Bone marrowderived, endothelial progenitorlike cells as angiogenesisselective genetargeting vectors ［J］. Gene Therapy, 2003, 10(8): 647-656.

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［12］ TateishiYuyama E, Matsubara H, Murohara T, et al. Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bonemarrow cells:a pilot study and a randomised controlled trial ［J］. Lancet, 2002, 360(9331):427-435.

备注/Memo

备注/Memo:
收稿日期：2006-09-11.基金项目：国家自然科学基金项目资助(No.30170365) 通讯作者：王彬尧， 主任医师， 主要从事冠心病的预防和治疗研究Email:wbinyao@163.com王长谦,主任医师， 主要从事动脉粥样硬化的发生机制研究Email:wchangqian@163.com 作者简介：姜萌, 主治医师, 博士Email:jiangmeng0919@163.com
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