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Endothelial alpha-parvin controls integrity of developing vasculature and is required for maintenance of cell-cell junctions

Authors

  • A. Fraccaroli
  • B. Pitter
  • A.A. Taha
  • J. Seebach
  • S. Huveneers
  • J. Kirsch
  • R.P. Casaroli-Marano
  • S. Zahler
  • U. Pohl
  • H. Gerhardt
  • H.J. Schnittler
  • E. Montanez

Journal

  • Circulation Research

Citation

  • Circ Res 117 (1): 29-40

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.


DOI

doi:10.1161/CIRCRESAHA.117.305818