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Cardiovascular Research 2004 64(3):421-430; doi:10.1016/j.cardiores.2004.07.012
© 2004 by European Society of Cardiology
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Copyright © 2004, European Society of Cardiology

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

Xu Penga, Hiroki Uedaa, Hongming Zhoub, Tracy Stokola,c, Tang-Long Shena, Ana Alcarazd, Tamas Nagya, Jean-Dominique Vassallib and Jun-Lin Guana,*

aDepartment of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA
bDepartment of Morphology, Medical Faculty of University of Geneva, Geneva, Switzerland
cDepartment of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA
dDepartment of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA

* Corresponding author. Tel.: +1 (607) 253 3586; fax: (607) 253 3708. Email address: jg19{at}cornell.edu

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 overexpressed 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.

KEYWORDS Focal adhesion kinase; Angiogenesis; Transgenic mouse; Endothelial cells

Time for primary review 18 days


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