内质网Ca2+感受器STIM1调控糖尿病冠状动脉平滑肌细胞表型转化的机制

项目名称： 内质网Ca2+感受器STIM1调控糖尿病冠状动脉平滑肌细胞表型转化的机制

项目编号： No.81470440

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 邓春玉

作者单位： 广东省心血管病研究所

项目金额： 68万元

中文摘要： 血管平滑肌细胞(VSMCs)表型转化是糖尿病动脉粥样硬化形成的关键环节，但其机制不明。既往研究提示与钙调控异常导致VSMCs收缩型和合成型蛋白表达失平衡有关，我们预实验发现糖尿病冠状动脉组织Ca2+感受器STIM1表达显著升高；VSMCs上调STIM1可增加骨桥蛋白表达，同时抑制SM22α、α-SMA和SM-MHC表达，促进细胞增殖，推测STIM1可调控糖尿病VSMCs表型转化。本研究拟首先明确STIM1在糖尿病VSMCs表型转化过程中的作用，并阐明STIM1通过Orai1/Calcineurin/NFAT（合成型）和L-型钙通道/myocardin/SRF（收缩型）钙信号通路调控VSMCs表型标志蛋白表达的分子机制，最后探讨STIM1敲除对糖尿病冠状动脉VSMCs表型转化的影响。该研究工作将较系统地认识STIM1调控VSMCs表型转化的分子机制，为多途径防治糖尿病冠心病提供新的理论依据。

中文关键词： 血管平滑肌细胞；糖尿病；冠状动脉；钙调控；STIM1

英文摘要： Vascular smooth muscle cells (VSMCs) phenotype transformation is the key to the formation of atherosclerosis in diabetes, but the mechanism is unknown. Previous studies have demonstrated that calcium regulation dysfunction induced the imbalance of VSMCs contractile proteins and synthetic proteins expression. The pre experiment found that Ca2+ sensor STIM1 expression was significantly increased in diabetic arterial coronary tissue; In VSMCs upregulation of STIM1 can increase osteopontin expression, inhibit SM22 α, α -SMA and SM-MHC expression, and promote cell proliferation, suggesting that STIM1 can regulate the phenotype of diabetic VSMCs. This study was firstly identified the role of STIM1 in diabetes VSMCs phenotypic transformation process and clarified the STIM1 by Orai1/Calcineurin/NFAT (synthetic) and L-type calcium channel / myocardin / SRF (contractile) calcium signaling pathway in VSMCs table molecular mechanisms marker protein expression, and finally explored STIM1 knockout on diabetic coronary VSMCs phenotypic transformation.The research work will be more systematic understanding of the molecular mechanisms of STIM1 regulating phenotypic transformation of VSMCs for diabetes prevention and treatment of coronary heart disease and more ways to provide a new theoretical basis.

英文关键词： Vascular smooth muscle cells;Diabetes;Coronary artery;Calcium handling;STIM1