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          Institute: MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut)     Collection: Yearbook 2016     Display Documents



ID: 723923.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Yearbook 2016
Endothelial Galphaq/11 is required for VEGF-induced vascular permeability and angiogenesis
Authors:Sivaraj, K. K.; Li, R.; Albarran-Juarez, J.; Wang, S.; Tischner, D.; Grimm, M.; Swiercz, J. M.; Offermanns, S.; Wettschureck, N.
Date of Publication (YYYY-MM-DD):2015-10-01
Title of Journal:Cardiovasc Res
Volume:108
Issue / Number:1
Start Page:171
End Page:180
Audience:Not Specified
Abstract / Description: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.
Free Keywords:Angiogenesis; Gq/11 family; Heterotrimeric G-proteins; Permeability; VEGF receptor 2
External Publication Status:published
Document Type:Article
Communicated by:n.n.
Affiliations:MPI für physiologische und klinische Forschung
External Affiliations:Department of Pharmacology, Max Planck Institute for Heart and Lung Research, Ludwigstrasse 43, 61231 Bad Nauheim, Germany J.W. Goethe University Frankfurt, 60590 Frankfurt, Germany. Department of Pharmacology, Max Planck Institute for Heart and Lung Research, Ludwigstrasse 43, 61231 Bad Nauheim, Germany J.W. Goethe University Frankfurt, 60590 Frankfurt, Germany nina.wettschureck@mpi-bn.mpg.de.
Identifiers:ISSN:1755-3245 (Electronic) 0008-6363 (Linking) %R 10.1093/cvr/cvv216
URL:http://www.ncbi.nlm.nih.gov/pubmed/26272756
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