| First Author | Fraccaroli A | Year | 2015 |
| Journal | Circ Res | Volume | 117 |
| Issue | 1 | Pages | 29-40 |
| PubMed ID | 25925587 | Mgi Jnum | J:249178 |
| Mgi Id | MGI:6098833 | Doi | 10.1161/CIRCRESAHA.117.305818 |
| Citation | Fraccaroli A, et al. (2015) Endothelial alpha-parvin controls integrity of developing vasculature and is required for maintenance of cell-cell junctions. Circ Res 117(1):29-40 |
| abstractText | 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 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 because of 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-extracellular matrix adhesion structures and an altered actin cytoskeleton. CONCLUSIONS: Endothelial alpha-pv is essential for vessel sprouting and for vessel stability. |
