Endothelial Gαq/11 is required for VEGF-induced vascular permeability and angiogenesis. (13th August 2015)

• Record Type: Journal Article
• Authors: Sivaraj, Kishor K.; Li, Rui; Albarran-Juarez, Julian; Wang, Shengpeng; Tischner, Denise; Grimm, Myriam; Swiercz, Jakub M.; Offermanns, Stefan; Wettschureck, Nina
• Is Part Of: Cardiovascular research. Volume 108:Number 1(2015)
• Page Start: 171
• Page End: 180
• Publication Date: 2015-08-13
• Subjects: Heterotrimeric G-proteins -- Gq/11 family -- VEGF receptor 2 -- Permeability -- Angiogenesis; Cardiovascular system -- Diseases -- Periodicals; Cardiovascular system -- Periodicals; 616.1
• DOI: 10.1093/cvr/cvv216
• Languages: English
• ISSNs: 0008-6363

Abstract

Abstract: 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 Gαq/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 Gαq/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 Gαq/11 -dependent manner, thereby enhancing downstream VEGFR2 signalling. In vivo, EC-specific Gαq/11 - and Gαq -deficient mice showed reduced VEGF-induced fluid extravasation, and retinal angiogenesis was significantly impaired. Gαq -deficient ECs showed reduced proliferation, Cdh5 phosphorylation, and fluid extravasation, whereas apoptosis was increased. Conclusion: Gαq/11 critically contributes to VEGF-A-dependent permeability control and angiogenic behaviour in vitro and in vivo .