Epac1 promotes neointimal thickening via calcium/calcineurin-dependent smooth muscle cell polarization and migration after vascular injury.

点击翻译按钮获取中文摘要

Vascular remodeling after mechanoinjury largely depends on migration of aortic smooth muscle cell (ASMC). We have reported that activation of exchange protein activated by cAMP 1 (Epac1) promotes ASMC migration. However, the role of Epac1 in advancing vascular remodeling upon vascular injury in vivo, and the intracellular mechanisms remain unknown.PDGF-BB-induced directional migration of Epac1KO ASMCs was significantly decreased. PDGF-BB-mediated intracellular Ca2+ elevation of Epac1KO ASMCs was significantly reduced. To assess the establishment of cell polarization under stimulation with PDGF-BB,activation of cofilin in Epac1KO ASMCs was significantly degreased. Activation of cofilin in WT ASMCs was suppressed by cyclosporine A, a calcineurin inhibitor. Ratio intimal thickening to smooth muscle layer of Epac1KO was significantly lower than that of WT.These results suggest that Epac1 promotes directional migration of ASMC via calcium/calcineurin-mediated activation of cofilin.