Beschreibung:
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<jats:title>
<jats:underline>Rationale:</jats:underline>
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<jats:p>Angiogenesis and vessel integrity depend on the adhesion of endothelial cells (ECs) to the extracellular matrix and to adjacent ECs. The focal adhesion protein α-parvin (α-pv) is essential for vascular development. However, the role of α-pv in ECs in vivo is not known.</jats:p>
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<jats:title>
<jats:underline>Objective:</jats:underline>
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<jats:p>To determine the function of α-pv in ECs during vascular development in vivo and the underlying mechanisms.</jats:p>
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<jats:title>
<jats:underline>Methods and Results:</jats:underline>
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<jats:p>
We deleted the
<jats:italic>α-pv</jats:italic>
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.
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<jats:underline>Conclusions:</jats:underline>
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<jats:p>Endothelial α-pv is essential for vessel sprouting and for vessel stability.</jats:p>
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