| First Author | Sivaraj KK | Year | 2015 |
| Journal | Cardiovasc Res | Volume | 108 |
| Issue | 1 | Pages | 171-80 |
| PubMed ID | 26272756 | Mgi Jnum | J:259659 |
| Mgi Id | MGI:6142554 | Doi | 10.1093/cvr/cvv216 |
| Citation | Sivaraj KK, et al. (2015) Endothelial Galphaq/11 is required for VEGF-induced vascular permeability and angiogenesis. Cardiovasc Res 108(1):171-80 |
| abstractText | AIMS: VEGF A (VEGF-A) is a central regulator of pre- and postnatal vascular development. In vitro studies suggested that heterotrimeric G-proteins of the Gq/11 family contribute to VEGF receptor 2 (VEGFR2) signalling, but the mechanism and physiological relevance of this finding is unknown. The aim of this study is to understand the role of endothelial Galphaq/11 in VEGF-dependent regulation of vascular permeability and angiogenesis. METHODS AND RESULTS: We show here that VEGF-A-induced signalling events, such as VEGFR2 autophosphorylation, calcium mobilization, or phosphorylation of Src and Cdh5, were reduced in Galphaq/11-deficient endothelial cells (ECs), resulting in impaired VEGF-dependent barrier opening, tube formation, and proliferation. Agonists at Gq/11-coupled receptors facilitated VEGF-A-induced VEGFR2 autophosphorylation in a Galphaq/11-dependent manner, thereby enhancing downstream VEGFR2 signalling. In vivo, EC-specific Galphaq/11- and Galphaq-deficient mice showed reduced VEGF-induced fluid extravasation, and retinal angiogenesis was significantly impaired. Galphaq-deficient ECs showed reduced proliferation, Cdh5 phosphorylation, and fluid extravasation, whereas apoptosis was increased. CONCLUSION: Galphaq/11 critically contributes to VEGF-A-dependent permeability control and angiogenic behaviour in vitro and in vivo. |
