The FGF system has a key role in regulating vascular integrity.
The integrity of the endothelial monolayer is essential to blood vessel homeostasis and active regulation of endothelial permeability. The FGF system plays important roles in a wide variety of physiologic and pathologic conditions; however, its role in the adult vasculature has not been defined. To assess the role of the FGF system in the adult endothelial monolayer, we disrupted FGF signaling in bovine aortic endothelial cells and human saphenous vein endothelial cells in vitro and in adult mouse and rat endothelial cells in vivo using soluble FGF traps or a dominant inhibitor of all FGF receptors. The inhibition of FGF signaling using these approaches resulted in dissociation of the VE-cadherin/p120-catenin complex and disassembly of adherens and tight junctions, which progressed to loss of endothelial cells, severe impairment of the endothelial barrier function, and finally, disintegration of the vasculature. Thus, FGF signaling plays a key role in the maintenance of vascular integrity.
Murakami
Masahiro
M
Angiogenesis Research Center and Section of Cardiology, Dartmouth Medical School, Lebanon, New Hampshire, USA.
Nguyen
Loc T
LT
Zhuang
Zhen W
ZW
Zhang
Zhen W
ZW
Moodie
Karen L
KL
Carmeliet
Peter
P
Stan
Radu V
RV
Simons
Michael
M
D022005:Adherens Junctions / Q000378:metabolism; D000818:Animals; D001808:Blood Vessels / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism; D002199:Capillary Permeability / Q000502:physiology; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D005346:Fibroblast Growth Factors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D051379:Mice; D051381:Rats; D015398:Signal Transduction; D013997:Time Factors
D015820:Cadherins; D005346:Fibroblast Growth Factors
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