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

内皮细胞 α-parvin 控制发育血管的完整性,并且是维持细胞间连接所必需的

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作者:Alessia Fraccaroli, Bettina Pitter, Abdallah Abu Taha, Jochen Seebach, Stephan Huveneers, Julian Kirsch, Ricardo P Casaroli-Marano, Stefan Zahler, Ulrich Pohl, Holger Gerhardt, Hans-J Schnittler, Eloi Montanez

Conclusions

Endothelial α-pv is essential for vessel sprouting and for vessel stability.

Objective

To determine the function of α-pv in ECs during vascular development in vivo and the underlying mechanisms.

Results

We deleted the α-pv gene specifically in ECs of mice to study its role in angiogenesis and vascular development. Here, we show that endothelial-specific deletion of α-pv in mice results in late embryonic lethality associated with hemorrhages and reduced vascular density. Postnatal-induced EC-specific deletion of α-pv leads to retinal hypovascularization because of reduced vessel sprouting and excessive vessel regression. In the absence of α-pv, blood vessels display impaired VE-cadherin junction morphology. In vitro, α-pv-deficient ECs show reduced stable adherens junctions, decreased monolayer formation, and impaired motility, associated with reduced formation of integrin-mediated cell-extracellular matrix adhesion structures and an altered actin cytoskeleton. Conclusions: Endothelial α-pv is essential for vessel sprouting and for vessel stability.

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