醛固酮对心血管系统的损害为国内外研究的热点。我们前期研究发现，醛固酮（Aldo）在体内诱导主动脉血管平滑肌细胞(VSMC)凋亡和细胞外基质蛋白Fibulin-5沉积。与fibronectin类似，Fibulin-5也可以与β1-integrin结合影响细胞生存，其可能是Aldo诱导VSMC凋亡的重要介质。本项目拟首先观察Aldo在体外对VSMC凋亡的影响；然后转染fibulin-5表达载体或siRNA质粒，使VSMC过表达或沉默Fibulin-5，观察Fibulin-5在Aldo诱导VSMC凋亡中的作用；随后,加入fibronectin,验证Fibulin-5与fibronectin功能上的竞争关系；最后应用β1-integrin激活或抑制抗体，观察Fibulin-5对β1-integrin信号通路的影响，从而系统揭示Fibulin-5在Aldo诱导VSMC凋亡中的作用及其机制。

Primary aldosteronism is the most common reason of secondary hypertension. Adrenal aldosterone-producing adenoma (APA), the most important type of primary aldosteronism, is treated mainly by surgical resection. However, even though APA is removed, a part of patients still suffer from resistant hypertension possibly due to irreversible vascular remodeling, the exact mechanism of which is still unclear. Aldosterone-induced cardiovascular damage is currently a hot research at home and abroad. Our previous study found that aldosterone induced both apoptosis of vascular smooth muscle cells(VSMCs) and extracelluar matrix protein Fibulin-5 deposition in the aorta in vivo. Similar to fibronectin, Fibulin-5 can affect cell survival by combining with β1-integrin via its RGD motif, and may play an important role in aldosterone-induced VSMC apoptosis. In the present project, the effect of aldosterone on VSMC apoptosis in vitro will be first observed; then, Fibulin-5 overexpression or suppression in VSMCs is achieved by transfecting Fibulin-5 eukaryotic expression vector or fibulin-5 siRNA plasmid to observe the effect of Fibulin-5 on aldosterone-induced VSMC apoptosis; next, adding fibronectin to the experimental environment to verify the competitive relationship in function between Fibulin-5 and fibronectin; finally, the effect of Fibulin-5 on β1-integrin signal pathway is examined by using β1-integrin inhibitory or stimulatory antibodies, in order to systematically reveal the effect of Fibulin-5 on aldosterone-induced VSMC apoptosis and the mechanism wherein.