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


METHODS
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.


CONCLUSIONS
These results indicate that FAK may play an important role in the promotion of angiogenesis in vivo.
Peng
Xu
X
Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
Ueda
Hiroki
H
Zhou
Hongming
H
Stokol
Tracy
T
Shen
Tang-Long
TL
Alcaraz
Ana
A
Nagy
Tamas
T
Vassalli
Jean-Dominique
JD
Guan
Jun-Lin
JL
D000818:Animals; D002196:Capillaries; D002465:Cell Movement; D002645:Chickens; D042783:Endothelial Cells / Q000201:enzymology*; D004730:Endothelium, Vascular / Q000201:enzymology*; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D015870:Gene Expression; D006614:Hindlimb; D006801:Humans; D007511:Ischemia; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D018482:Muscle, Skeletal / Q000098:blood supply; D018919:Neovascularization, Physiologic; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D042787:Receptor, TIE-2 / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology*; D014945:Wound Healing
D011505:Protein-Tyrosine Kinases; D042787:Receptor, TIE-2; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; C496051:Ptk2 protein, mouse