title: Stim1- and Orai1-mediated store-operated calcium entry is critical for angiotensin II-induced vascular smooth muscle cell proliferation.
abstract: OBJECTIVE
  Despite the fact that angiotensin (Ang) II is a critical regulator of the proliferation and migration of vascular smooth muscle cells (VSMCs), the effect of Ang II on VSMC proliferation has remained unclear. In this study, we determined whether Stim1- and Orai1-mediated store-operated calcium (Ca(2+)) entry (SOCE) plays a critical role in Ang II-induced VSMC proliferation and Ang II-accelerated neointimal growth after balloon injury of rat carotid arteries.
  
  
  RESULTS
  Knockdown of Stim1 and Orai1, putative calcium sensors/modulators, suppressed Ang II-mediated Ca(2+) entry and cell proliferation in synthetic VSMCs. Stim1 and Orai1 short interfering RNAs (siRNAs) decreased neointimal growth induced by Ang II in balloon-injured rat carotid arteries. Ang II signiﬁcantly increased the expression of Stim1 and Orai1 in neointima. In addition, our results showed that receptor subtype-1 (AT1) significantly contributed to Ang II-induced Ca(2+) entry and proliferation of synthetic VSMCs. However, we found that transient receptor potential canonical 1 (Trpc1) had no effect on Ang II-induced SOCE or cell proliferation of synthetic VSMCs.
  
  
  CONCLUSIONS
  We show for the first time that Stim1- and Orai1-mediated SOCE may be critical for Ang II-induced VSMC proliferation. This provides important information with respect to targeting cardiovascular diseases under the enhanced renin-Ang system.
authors: Department of Cardiology,  Kunming General Hospital of Chengdu Military Area, Yunnan 650032,  China.
authors: Rui-wei
authors: RW
authors: Guo
authors: Li-xia
authors: LX
authors: Yang
authors: Mao-quan
authors: MQ
authors: Li
authors: Xing-hua
authors: XH
authors: Pan
authors: Bei
authors: B
authors: Liu
authors: Yong-li
authors: YL
authors: Deng
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects*; D008297:Male; D008562:Membrane Glycoproteins / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000071740:ORAI1 Protein; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology; D000071737:Stromal Interaction Molecule 1
chemical_list: D015220:Calcium Channels; D008562:Membrane Glycoproteins; D000071740:ORAI1 Protein; C532493:Orai1 protein, rat; D044140:Receptor, Angiotensin, Type 1; C518857:Stim1 protein, rat; D000071737:Stromal Interaction Molecule 1; D000804:Angiotensin II; D002118:Calcium