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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., Pitter, B., Taha, A.A., Seebach, J., Huveneers, S., Kirsch, J., Casaroli-Marano, R.P., Zahler, S., Pohl, U., Gerhardt, H., 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 |
| 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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