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|本期目录/Table of Contents|

低氧诱导因子促缺血下肢血管新生的可行性研究(PDF)

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2008年第1期
页码:
28-33
栏目:
基础研究
出版日期:
2008-01-20

文章信息/Info

Title:
Feasibility of hypoxia inducible factor gene transfer in endothelial progenitor cell for vascular regeneration
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 低氧诱导因子1α (Hypoxia inducible factor1α, HIF1α)是低氧环境中起细胞调控作用的关键基因。 探讨HIF1α在细胞中的过表达是否有利于缺血性疾病的治疗。方法 在体外通过腺病毒介导人HIF1α基因(AdHIF1α)入人外周血内皮祖细胞（endothelial progenitor cells, EPC），观察转染后EPC的扩增及迁移功能改变及其在裸鼠缺血下肢局部的促血管新生作用。结果 转染AdHIF1α后的EPC在体外细胞扩增数成倍增加，迁移功能改善(P<0.05)；移植异种AdHIF1αEPC至BALB/c鼠缺血下肢后可见外源性EPC定向作用于缺血部位。AdHIF1αEPC较对照组进一步促进体内毛细血管数目增加(P<0.05)，缺血面积减小(P<0.05)、缺血下肢的坏死/自体离断降低60%。结论 在体外，AdHIF1α感染后的EPC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 explore whether the overexpression of hypoxia inducible factor1α (HIF1α) is beneficial in cell therapy of hypoxiainduced ischemic disease. METHODS Adenovirus mediated human HIF1(AdHIF1) was transduced in human endothelial progenitor cells (EPC) in vitro. Heterologous EPC transduced with adenovirus encoding HIF1α were administered to Balb/c nude mice with hindlimb ischemia. RESULTS Augmented EPC proliferative activity and enhanced migration activity were seen in HIF1 treated EPC (P<0.05). and exogenous EPC homing was observed. In vitro HIF1transduced EPC contributed to neovascularization in vivo. Limb necrosis reduced by 60% neovascularization in comparison with that in control animals and neovascularization was improved. CONCLUSION In vitro, AdHIF1EPC gene transfer enhances EPC proliferation and migration. In vivo, genemodified EPC 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

［1］ 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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［3］ Bompais H, Chagraoui J, Canron X, et al. Human endothelial cells derived from circulating progenitors display specific functional properties compared with mature vessel wall endothelial cells ［J］. Blood, 2004, 103(7):2577-2584.

［4］ Manalo DJ, Rowan A, Lavoie T, et al. Transcriptional regulation of vascular endothelial cell responses to hypoxia by HIF1［J］. Blood, 2005, 105(2):659-669.

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［6］ Asahara T, Murohara T, Sullivan A, et al . Isolation of Putative Progenitor Endothelial Cells for Angiogenesis［J］. Science,1997, 275(5302):964-967.

［7］ Filleur S, Courtin A, AitSiAli S, et al. siRNAmediated inhibition of vascular endothelial growth factor severely limits tumor resistance to antiangiogenic thrombospondin1 and slows tumor vascularization and growth［J］. Cancer Res, 2003, 63(14): 3919-3922.

［8］ Iba O,Matsubara H,Nozawa Y, et al. Angiogenesis by implantation of peripheral blood mononuclear cells and platelets into ischemic limbs［J］. Circulation, 2002, 106(15):2019-2025.

［9］ Ceradini DJ, Kulkarni AR, Callaghan MJ, et al. Progenitor cell trafficking is regulated by hypoxic gradients through HIF1 induction of SDF1［J］. Nat Med,2004, 10(8):858-864.

［10］Abbott JD, Huang Y, Liu D, et al. Stromal cellderived factor1αlpha plays a critical role in stem cell recruitment to the heart after myocardial infarction but is not sufficient to induce homing in the absence of injury［J］. Circulation, 2004, 110(21):3300-3305.

［11］Ceradini DJ, Gurtner GC. Homing to hypoxia: HIF1 as a mediator of progenitor cell recruitment to injured tissue［J］. Trends Cardiovasc Med, 2005,15(2):57-63.

［12］Shyu KG, Wang MT, Wang BW, et al. Intramyocardial injection of naked DNA encoding HIF1αlpha/VP16 hybrid to enhance angiogenesis in an acute myocardial infarction model in the rat［J］. Cardiovasc Res, 2002, 54(3):576-583.

备注/Memo

备注/Memo:
收稿日期：2007-01-04.基金项目：国家自然科学基金项目资助(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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