| First Author | Pitter B | Year | 2018 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 38 |
| Issue | 5 | Pages | 1147-1158 |
| PubMed ID | 29567677 | Mgi Jnum | J:285135 |
| Mgi Id | MGI:6385442 | Doi | 10.1161/ATVBAHA.118.310840 |
| Citation | Pitter B, et al. (2018) Parvins Are Required for Endothelial Cell-Cell Junctions and Cell Polarity During Embryonic Blood Vessel Formation. Arterioscler Thromb Vasc Biol 38(5):1147-1158 |
| abstractText | 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: alpha-pv (alpha-parvin) and beta-pv (beta-parvin). Recently, we have shown that alpha-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 alpha-pv in ECs in global beta-pv(-/-) mice (alpha-pv(DeltaEC);beta-pv(-/-) mice). Here, we show that alpha-pv(DeltaEC);beta-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 alpha-pv(DeltaEC);beta-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. |
