The FGF system has a key role in regulating vascular integrity
Masahiro Murakami, … , Radu V. Stan, Michael Simons
Masahiro Murakami, … , Radu V. Stan, Michael Simons
Published September 5, 2008
Citation Information: J Clin Invest. 2008;118(10):3355-3366. https://doi.org/10.1172/JCI35298.
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The FGF system has a key role in regulating vascular integrity

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.

Authors

Masahiro Murakami, Loc T. Nguyen, Zhen W. Zhang, Karen L. Moodie, Peter Carmeliet, Radu V. Stan, Michael Simons

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Figure 4

Effect of FGF inhibition in the endothelium: electron microscopy analyses.

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Effect of FGF inhibition in the endothelium: electron microscopy analyse...
(A) SEM analysis of rat femoral arteries transduced with Ad-Null. The arterial wall shows ridges formed due to contractions in the underlying smooth muscle cells (top panel, scale bar: 50 μm). Higher magnification detail of the Ad-Null–infected artery demonstrates the continuous endothelial monolayer (bottom panel, scale bar: 10 μm). (B) SEM analysis of Ad-FGFR1DN–transduced rat femoral artery. The area with remaining endothelial cells is shown (left panels, scale bars: 50 μm [top]; 10 μm [bottom]). Endothelial cells are swollen and have lost contacts with neighboring cells. Underlying matrix layer is partially exposed (white arrows). Area demonstrating severe loss of the endothelium with exposure of the subjacent basement membrane is also shown (right panels, scale bar: 50 μm [top]). Higher magnification shows a few cells, presumably platelets by size, adhering to the vessel wall (white arrowheads) (right panels, scale bar: 10 μm [bottom]). (C) Transmission electron microscopy analysis of Ad-Null–transduced rat femoral artery (day 2). Adjacent endothelial cells form a tightly sealed junction indicated by black arrows. Scale bar: 500 nm. (D) Ad-FGFR1DN–transduced artery (day 1). Scale bar: 2 μm. Inset: a gap is formed between endothelial cells. Arrow (inset) indicates open cell-cell junction. Scale bar: 500 nm. (E) Ad-FGFR1DN–transduced artery (day 2) shows an open endothelial junction (black arrows). A platelet (PLT) adheres to the open space and extends a cellular process (white arrowhead). Scale bar: 500 nm. (F) Ad-FGFR1DN–transduced artery showing a wide gap in the endothelium (black arrow) and an EC detaching from the basement membrane. Scale bar: 2 μm.