title: RGS5 promotes arterial growth during arteriogenesis.
abstract: Arteriogenesis-the growth of collateral arterioles-partially compensates for the progressive occlusion of large conductance arteries as it may occur as a consequence of coronary, cerebral or peripheral artery disease. Despite being clinically highly relevant, mechanisms driving this process remain elusive. In this context, our study revealed that abundance of regulator of G-protein signalling 5 (RGS5) is increased in vascular smooth muscle cells (SMCs) of remodelling collateral arterioles. RGS5 terminates G-protein-coupled signalling cascades which control contractile responses of SMCs. Consequently, overexpression of RGS5 blunted Gαq/11-mediated mobilization of intracellular calcium, thereby facilitating Gα12/13-mediated RhoA signalling which is crucial for arteriogenesis. Knockdown of RGS5 evoked opposite effects and thus strongly impaired collateral growth as evidenced by a blockade of RhoA activation, SMC proliferation and the inability of these cells to acquire an activated phenotype in RGS5-deficient mice after the onset of arteriogenesis. Collectively, these findings establish RGS5 as a novel determinant of arteriogenesis which shifts G-protein signalling from Gαq/11-mediated calcium-dependent contraction towards Gα12/13-mediated Rho kinase-dependent SMC activation.
authors: Division of Cardiovascular Physiology, Institute of Physiology and Pathophysiology, University of Heidelberg, Heidelberg, Germany.
authors: Caroline
authors: C
authors: Arnold
authors: Division of Cardiovascular Physiology, Institute of Physiology and Pathophysiology, University of Heidelberg, Heidelberg, Germany.
authors: Anja
authors: A
authors: Feldner
authors: Division of Cardiovascular Physiology, Institute of Physiology and Pathophysiology, University of Heidelberg, Heidelberg, Germany.
authors: Larissa
authors: L
authors: Pfisterer
authors: Division of Cardiovascular Physiology, Institute of Physiology and Pathophysiology, University of Heidelberg, Heidelberg, Germany.
authors: Maren
authors: M
authors: Hödebeck
authors: Department of Pharmacology, Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany.
authors: Kerstin
authors: K
authors: Troidl
authors: Division of Vascular Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors: Guillem
authors: G
authors: Genové
authors: Institute of Experimental and Clinical Pharmacology and Toxicology, University of Heidelberg, Mannheim, Germany.
authors: Thomas
authors: T
authors: Wieland
authors: Division of Cardiovascular Physiology, Institute of Physiology and Pathophysiology, University of Heidelberg, Heidelberg, Germany.
authors: Markus
authors: M
authors: Hecker
authors: Division of Cardiovascular Physiology, Institute of Physiology and Pathophysiology, University of Heidelberg, Heidelberg, Germany korff@physiologie.uni-heidelberg.de.
authors: Thomas
authors: T
authors: Korff
mesh_terms: D000818:Animals; D001160:Arterioles / Q000254:growth & development*; D049109:Cell Proliferation; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000378:metabolism; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000378:metabolism; D055785:Gene Knockdown Techniques; D051379:Mice; D018345:Mice, Knockout; D032389:Myocytes, Smooth Muscle / Q000502:physiology; D020710:RGS Proteins / Q000235:genetics / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D020710:RGS Proteins; C105346:Rgs5 protein, mouse; D044365:GTP-Binding Protein alpha Subunits, G12-G13; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D020742:rhoA GTP-Binding Protein
keywords: G‐protein; RGS5; arteriogenesis; remodelling; vascular smooth muscle cells