冠心病发病中Egr3/VEGF调控动脉粥样硬化斑块形成的分子机制研究

炎症反应和血管新生是动脉粥样硬化性疾病重要的病理学特征。申请者前期利用人类全基因组表达谱芯片对新疆不同民族冠心病发病相关的差异基因进行筛选，发现Egr3基因在维吾尔族冠心病和汉族冠心病间的表达存在差异，Egr3基因突变可显著增加冠心病的患病风险，但其机制尚不清楚。课题组前期预实验提示动脉粥样硬化模型小鼠斑块内Egr3 mRNA及蛋白表达水平显著上调。本研究拟采用动脉粥样硬化模型，敲除体内体外Egr3基因，从细胞、整体及临床人群三个水平，采用CRISPR/Cas9基因编辑、AAV9病毒靶向转导、ELISA、CHIP、IP、油红O染色、流式细胞术、Real time -PCR、Western blot等分子生物学手段，阐明Egr3/VEGF调控炎症反应和血管新生在动脉粥样硬化斑块形成中的分子机制，为冠心病的早期防控提供重要的理论依据。

Inflammation and angiogenesis are the important pathological features of atherosclerotic diseases. In our previously study, we using gene chip expression profiles to explore the differential gene expression among different ethnic patients with coronary artery disease in Xinjiang, we found that there was significant difference of Egr3 expression between Han and Uyghur coronary artery disease patients and Egr3 gene mutation can significantly increase the risk of coronary artery disease, but the mechanism is still unknown. our preliminary data also showed that the expression of Egr3 was significantly increased in atherosclerotic plaque. The study aimed to investigate the mechanisms of regulating the inflammation and angiogenesis of Egr3/VEGF in atherosclerosis by using CRISPR/Cas9 gene editing technology, AAV9 virus targeting transduction, ELISA, CHIP, IP, oil red O stain, flow cytometry, Real time –PCR and Western blot to provides important theoretical foundation for the early prevention and contain of coronary artery disease.