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Endothelial alpha-parvin controls integrity of developing vasculature and is required for maintenance of cell-cell junctions

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Item Type:Article
Title:Endothelial alpha-parvin controls integrity of developing vasculature and is required for maintenance of cell-cell junctions
Creators Name:Fraccaroli, A. and Pitter, B. and Taha, A.A. and Seebach, J. and Huveneers, S. and Kirsch, J. and Casaroli-Marano, R.P. and Zahler, S. and Pohl, U. and Gerhardt, H. and Schnittler, H.J. and Montanez, E.
Abstract:RATIONALE: Angiogenesis and vessel integrity depend on the adhesion of endothelial cells (EC) to the extracellular matrix (ECM) and to adjacent ECs. The focal adhesion protein alpha-parvin (alpha-pv) is essential for vascular development. However, the role of alpha-pv in ECs in vivo is not known. OBJECTIVE: To determine the function of alpha-pv in ECs during vascular development in vivo and the underlying mechanisms. METHODS AND RESULTS: We deleted the alpha-pv gene specifically in ECs of mice to study its role in angiogenesis and vascular development. Here we show that endothelial-specific deletion of alpha-pv in mice results in late embryonic lethality associated with hemorrhages and reduced vascular density. Postnatal induced EC-specific deletion of alpha-pv leads to retinal hypovascularization due to reduced vessel sprouting and excessive vessel regression. In the absence of alpha-pv, blood vessels display impaired VE-cadherin junction morphology. In vitro, alpha-pv deficient ECs show reduced stable adherens junctions, decreased monolayer formation and impaired motility, associated with reduced formation of integrin-mediated cell-ECM adhesion structures and an altered actin cytoskeleton. CONCLUSIONS: Endothelial alpha-pv is essential for vessel sprouting and for vessel stability.
Keywords:Integrin, Alpha-Parvin, Intercellular Junction, Angiogenesis, Vessel Stability, Angiogenesis, Blood Vessel, Cell Adhesion Molecule, Development, Embryonic Development, Animals, Mice
Source:Circulation Research
ISSN:0009-7330
Publisher:American Heart Association (U.S.A.)
Volume:117
Number:1
Page Range:29-40
Date:19 June 2015
Additional Information:Copyright © 2015 The Authors
Official Publication:https://doi.org/10.1161/CIRCRESAHA.117.305818
PubMed:View item in PubMed

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