Journal
CIRCULATION RESEARCH
Volume 117, Issue 1, Pages 29-40Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCRESAHA.117.305818
Keywords
adherens junctions; angiogenesis; blood vessels; cell adhesion molecules; growth and development
Funding
- DFG [MO2562/1-1, INST2105/24-1, SCH430/6-2]
- Bioimaging Network of the Ludwig-Maximilians University Munich (LMU innovative)
- Munich Cluster for Systems Neurology (SyNergy)
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Rationale: Angiogenesis and vessel integrity depend on the adhesion of endothelial cells (ECs) to the extracellular matrix and to adjacent ECs. The focal adhesion protein -parvin (-pv) is essential for vascular development. However, the role of -pv in ECs in vivo is not known. Objective: To determine the function of -pv in ECs during vascular development in vivo and the underlying mechanisms. Methods and Results: We deleted the -pv gene specifically in ECs of mice to study its role in angiogenesis and vascular development. Here, we show that endothelial-specific deletion of -pv in mice results in late embryonic lethality associated with hemorrhages and reduced vascular density. Postnatal-induced EC-specific deletion of -pv leads to retinal hypovascularization because of reduced vessel sprouting and excessive vessel regression. In the absence of -pv, blood vessels display impaired VE-cadherin junction morphology. In vitro, -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 -pv is essential for vessel sprouting and for vessel stability.
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