Overexpression of focal adhesion kinase in vascular endothelial cells promotes angiogenesis in transgenic mice

被引:91
作者
Peng, X
Ueda, H
Zhou, HM
Stokol, T
Shen, TL
Alcaraz, A
Nagy, T
Vassalli, JD
Guan, JL [1 ]
机构
[1] Cornell Univ, Coll Vet Med, Dept Mol Med, Ithaca, NY 14853 USA
[2] Univ Geneva, Fac Med, Dept Morphol, Geneva, Switzerland
[3] Cornell Univ, Coll Vet Med, Dept Populat Med & Diagnost Sci, Ithaca, NY 14853 USA
[4] Cornell Univ, Coll Vet Med, Dept Biomed Sci, Ithaca, NY 14853 USA
关键词
focal adhesion kinase; angiogenesis; transgenic mouse; endothelial cells;
D O I
10.1016/j.cardiores.2004.07.012
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective: Focal adhesion kinase is implicated in the regulation of cell adhesion, migration, survival, and cell-cycle progression. However, the functions of focal adhesion kinase in endothelial cell (EC) in vivo remain unclear. This study aims to examine the role of FAK in EC function and angiogenesis in vivo by transgenic mice approach. Method: We generated transgenic mice which overexpresscd chicken FAK in vascular endothelial cell under the control of the Tie-2 promoter and enhancer. FAK transgene was detected by RT-PCR, immunoprecipitation, and Western blot. The effect of FAK overexpression on angiogenesis was determined using skin Wound healing and ischemia skeleton muscle models. Results: Expression of FAK transgene was detected in all vessel-rich tissues. Expression of FAK protein was verified by antibody specific for the exogenous chicken FAK in lung homogenates and isolated EC. In the wound-induced angiogenesis model, the number of vessels in the granulation tissue of healing Wound was significantly increased in the transgenic mouse compared to that of wild-type control mice. Similarly, in the ischemia skeleton muscle model, the density of capillaries was significantly increased in the transgenic mouse. Conclusion: These results indicate that FAK may play an important role in the promotion of angiogenesis in vivo. (C) 2004 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:421 / 430
页数:10
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