我们已证实，细胞骨架相关蛋白SM22α是血管平滑肌细胞（VSMC）增殖信号通路Ras-ERK的负调节因子。近期的报道和我们的预实验结果均强烈提示，SM22α缺失与血管氧化应激和炎症损伤密切相关。鉴于PKC-p47phox轴在ROS生成中的关键作用，我们假设，SM22α通过调制PKC-p47phox轴活性而参与AngII诱导的血管氧化应激。为此，本项目拟确定SM22α与PKC-p47phox信号级联激活和ROS生成的相关性及可能的作用环节；探讨SM22α磷酸化与PKC, p47phox之间的互作关系和交谈模式；明确SM22α介导的actin动力学与PKC-p47phox轴激活的因果关联；用Sm22-/-小鼠分别建立继发性高血压和内膜增生模型，评价SM22α在体内抗氧化应激活性及病理生理学意义。为发掘SM22α的新功能和在血管损伤修复中的意义开辟新视角；为高血压防治提供新的思路和药物筛选靶标。

We have demonstrated that cytoskeleton-associated protein SM22α is negative regulator of Ras-ERK signaling pathway in VSMCs. Recent study suggested that the disruption of SM22α is associated with oxidative stress and inflammation in vascular injury. Based on pivotal roles of PKC-p47phox in ROS production, we suggest the hypothesis that SM22α is involved in AngII-induced vascular oxidative stress via modulating PKC-p47phox activity. The goal of the present project is to determine the correlation between SM22α and PKC-p47phox activation, the mechanism of their cross-talking and the interaction of each other. We are going to investigate whether SM22α-mediated actin dynamics is involved in PKC-p47phox activation and ROS production. Furthermore, the Sm22-/- mice will be used to establish the model of balloon injury or hypertension, which aim to evaluate the anti-oxidative stress action of SM22α in vivo. This study will elucidate novel function of SM22α in vascular injury, and provide a potential target for the development of new therapeutics for cardiovascular diseases.