Parvins Are Required for Endothelial Cell–Cell Junctions and Cell Polarity During Embryonic Blood Vessel FormationHighlights
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Objective—During vascular development, integrin-mediated signaling regulates the formation and stabilization of cell–cell junctions, which are required for endothelial cell (EC) apical–basal polarity and proper deposition of the vascular basement membrane. Parvins are actin-binding proteins that facilitate the interaction of integrins with the actin cytoskeleton. The endothelium expresses 2 parvin isoforms: α-pv (α-parvin) and β-pv (β-parvin). Recently, we have shown that α-pv is critical for vessel growth and vessel stability at late embryonic developmental stages. The role of parvins during early embryonic development is unknown.
Approach and Results—To investigate the role of endothelial parvins in the developing vasculature, we generated mice with ECs lacking both parvin isoforms by deleting α-pv in ECs in global β-pv−/− mice (α-pvΔEC;β-pv−/− mice). Here, we show that α-pvΔEC;β-pv−/− mice die around embryonic day 11.5 and exhibit hemorrhages, immature capillary beds, and severe vascular defects in the central nervous system, including reduced vessel branching, increased vessel diameter, and balloon-like hemorrhagic clusters of ECs. Vessels in α-pvΔEC;β-pv−/− embryos display disorganized cell–cell junctions, impaired endothelial apical–basal polarity, and discontinuous basement membranes. These vascular defects are accompanied by defective pericyte–vessel interaction.
Conclusions—Our results show that parvins are critical for the organization of endothelial cell–cell junctions, the establishment of endothelial apical–basal polarity, and the integrity of the basement membrane.
- Received September 29, 2017.
- Accepted March 5, 2018.
- © 2018 American Heart Association, Inc.