Document Type

Article

Publication Date

9-5-2008

Publication Title

Journal of Clinical Investigation

Department

Geisel School of Medicine

Abstract

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.

DOI

10.1172/JCI35298

Original Citation

Murakami M, Nguyen LT, Zhuang ZW, Moodie KL, Carmeliet P, Stan RV, Simons M. The FGF system has a key role in regulating vascular integrity. J Clin Invest. 2008 Oct;118(10):3355-66. doi: 10.1172/JCI35298. Erratum in: J Clin Invest. 2009 Jul;119(7):2113. Zhang, Zhen W [corrected to Zhuang, Zhen W]. PMID: 18776942; PMCID: PMC2528913.

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