Endothelial Alpha-Parvin Controls Integrity of Developing Vasculature and is Required for Maintenance of Cell-Cell Junctions
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 (α-pv) is essential for vascular development. However, the role of α-pv in ECs in vivo is not known.
Objective:To determine the function of α-pv in ECs during vascular development in vivo and the underlying mechanisms.
Methods and 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 due to 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-ECM adhesion structures and an altered actin cytoskeleton.
Conclusions: Endothelial α-pv is essential for vessel sprouting and for vessel stability.
- intercellular junction
- vessel stability
- blood vessel
- cell adhesion molecule
- embryonic development
- Received December 9, 2014.
- Revision received April 23, 2015.
- Accepted April 29, 2015.
Circulation Research is published on behalf of the American Heart Association, Inc., by Wolters Kluwer. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial-NoDervis License (http://creativecommons.org/licenses/by-nc-nd/3.0/), which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited, the use is noncommercial, and no modifications or adaptations are made.