Channelpedia

PubMed 25753987


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: TRP , TRPC , TRPC1



Title: Reduction of Store-Operated Ca(2+) Entry Correlates with Endothelial Progenitor Cell Dysfunction in Atherosclerotic Mice.

Authors: Lian-You Wang, Ji-Hang Zhang, Jie Yu, Jie Yang, Meng-Yang Deng, Hua-Li Kang, Lan Huang

Journal, date & volume: Stem Cells Dev., 2015 Jul 1 , 24, 1582-90

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/25753987


Abstract
The dysfunction of endothelial progenitor cells (EPCs) has been shown to prevent endothelial repair during the development of atherosclerosis (AS). Previous studies have revealed that store-operated calcium entry (SOCE) is an important factor in regulating EPC functions. However, whether this is also the mechanism in AS has not been elucidated. Therefore, we evaluated the role of SOCE in EPCs isolated from an atherosclerotic mouse model. Atheromatous plaques were more frequent in the aortas of ApoE(-/-) mice fed a high-fat diet for 16 weeks compared with controls, and the proliferative and migratory activities of atherosclerotic EPCs were significantly decreased. Accordingly, SOCE amplitude, as well as spontaneous or VEGF-induced Ca(2+) oscillations, decreased in atherosclerotic EPCs. These results may be associated with the downregulated expression of Stim1, Orai1, and TRPC1, which are major mediators of SOCE. In addition, eNOS expression and phosphorylation at Ser(1177), which are critical regulators of EPC function, were markedly reduced in the atherosclerotic EPCs. The impairment of eNOS activity could also be induced by using an SOCE inhibitor or by Stim1 gene silencing, indicating a link between the activities of eNOS and SOCE in AS. Furthermore, decreased SOCE function inhibited EPC proliferation and migration in vitro. In conclusion, our results showed that the reduction of SOCE induced EPC dysfunction during AS, potentially through downregulation of store-operated calcium channel (SOCC) components and impaired eNOS activity. Approaches aimed at reestablishing SOCE activity may thus improve the function of EPCs during AS.