| First Author | Arnold C | Year | 2014 |
| Journal | EMBO Mol Med | Volume | 6 |
| Issue | 8 | Pages | 1075-89 |
| PubMed ID | 24972930 | Mgi Jnum | J:232469 |
| Mgi Id | MGI:5779280 | Doi | 10.15252/emmm.201403864 |
| Citation | Arnold C, et al. (2014) RGS5 promotes arterial growth during arteriogenesis. EMBO Mol Med 6(8):1075-89 |
| abstractText | 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 Galphaq/11-mediated mobilization of intracellular calcium, thereby facilitating Galpha12/13-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 Galphaq/11-mediated calcium-dependent contraction towards Galpha12/13-mediated Rho kinase-dependent SMC activation. |
