主动脉瘤破裂是导致人类死亡的重要因素之一，全世界每年因腹主动脉瘤破裂致死的病例约有15万至20万例。主动脉瘤的发生主要伴随血管壁弹性蛋白及胞外基质降解，炎症细胞浸润增加，氧化应激反应加强等，而血管平滑肌细胞表型转化对于起始这些过程发挥了重要作用。NCoR1是一种转录调控辅因子，控制着细胞中大量基因的表达。我们着重研究平滑肌细胞中NCoR1的作用机制，以期探究其在主动脉瘤发生发展中的作用。通过分别构建平滑肌细胞特异性敲除和过表达NCoR1小鼠，并结合血管紧张素II诱导的主动脉瘤模型，观察NCoR1对主动脉瘤发生，瘤体破裂以及主动脉生理结构产生的影响。随后结合体外实验进一步研究NCoR1对平滑肌细胞表型转换，炎症以及氧化应激反应发生过程中的作用，并找寻其具体调控的分子机制。初步结果提示，平滑肌细胞敲除NCoR1可诱导平滑肌细胞由收缩型表型向合成型表型转换，促进动脉瘤的发生。

Aortic aneurysm rupture is an important cause of death in adults, which is estimated to lead to 150,000-200,000 deaths each year worldwide. Aortic aneurysm is characterized by proteolytic fragmentation of the ECM, immune cell infiltration of the adventitia and increased oxidative stress, smooth muscle cell phenotype modulation plays an important role in initiating those processes. NCoR1 is a transcriptional coregulator, which regulate a lot of genes expression in cells. Our study is aimed at exploring the role of smooth muscle cell NCoR1 in the pathogenesis of aortic aneurysms. By constructing smooth muscle cell NCoR1 knock out and overexpression mice in combination with AngiotensinII-induced aortic aneurysm mouse model, we are going to observe the morbidity and mortality of aortic aneurysms, and the pathological change of aorta. Then, by mechanism study we will figure out the role of NCoR1 in regulating the phenotype transformation, inflammation and oxidative stress in smooth muscle cells in vitro. Our preliminary result shows that smooth muscle cells NCoR1 knockout can induce contractile smooth muscle cells transforming into synthetic type and intend to aggravate aortic aneurysm.