醛固酮增多症导致心脑血管事件的风险明显升高，与内皮炎症密切相关。然而盐皮质激素受体拮抗剂却不能阻止心脑血管不良事件的进展。因此，为了提升药物治疗的有效性，进一步研究醛固酮造成血管损伤的机制极为必要。课题组前期发现，醛固酮可以增加GPER1和炎性分子的表达，给与GPER1受体阻断剂后炎性分子明显下降，从体外的角度证实了GPER1介导醛固酮引起内皮细胞炎性损伤，该现象或与s100A8通路相关。为了明确GPER1在醛固酮引起的血管炎性损伤中的作用及机制，课题组拟通过体内试验，建立内皮GPER1特异性敲除鼠，给与醛固酮干预后与野生型小鼠相比，观察血管炎症反应是否有所缓解，以及s100A8信号通路的变化；此外还将通过体外试验，建立s100A8低表达的内皮细胞模型，通过给与GPER1激动剂干预，分析基因型与野生型细胞炎性分子表达的变化，明确是s100A8是否介导GPER1作用。

Hyperaldosteronism leads to a significantly increased risk of cardiovascular and cerebrovascular disease as a result of endothelial inflammation. However, mineralocorticoid receptor antagonists cannot prevent the progression of cardiovascular and cerebrovascular adverse events. Therefore, in order to enhance the effectiveness of drug treatment, it is necessary to further study the mechanism of aldosterone related vascular injury. We have demonstrated that aldosterone could increase the inflammatory response as well as expression of GPER1 in cultured endothelial cells, and inflammatory response could be inhibited after GPER1 receptor antagonist. From an in vitro perspective, it was confirmed that GPER1 mediated aldosterone-induced inflammatory damage to endothelial cells. This phenomenon may be related to the s100A8 pathway. In order to clarify the role and mechanism of GPER1 in aldosterone-induced vascular inflammatory injury, we plans to establish endothelial GPER1 specific knockout mice in aminal experiments. After induction by aldosterone, we will compare knockout mice with wild-type mice, observe the severity of vascular inflammation, and analyze the changes in the s100A8 signaling pathway. In addition, another in vitro study will be established to generate an endothelial cell model with low expression of s100A8, and GPER1 agonist intervention will be given to analyze the changes in inflammatory response. In this way, we shall testify whether s100A8 mediates the effect of GPER1.