apM1基因局部调控心外膜脂肪-血管轴抗冠状动脉粥样硬化的分子机制

项目名称： apM1基因局部调控心外膜脂肪-血管轴抗冠状动脉粥样硬化的分子机制

项目编号： No.30872541

项目类型： 面上项目

立项/批准年度： 2009

项目学科： 生物科学

项目作者： 陈新忠

作者单位： 华中科技大学

项目金额： 31万元

中文摘要： 冠状动脉旁路移植术（CABG）不能逆转冠脉病变的进程，弥漫性狭窄、直径<1mm及心肌内冠脉粥样硬化的治疗及移植血管再狭窄的防治仍是冠脉外科难题之一。研究发现，内质网应激导致心外膜脂肪细胞内分泌功能的紊乱可触发冠状动脉粥样硬化，而目前抗冠心病治疗无法纠正其功能紊乱。冠心病心外膜脂肪脂联素分泌明显降低；脂联素由apM1基因表达，在脂肪-血管轴中起桥梁作用，抗动脉粥样硬化的形成。本课题组前期研究了脂肪-血管轴的脂肪细胞-巨噬细胞内分泌环中脂联素对巨噬细胞的调控：脂联素可抑制巨噬细胞活性。本课题从分子水平进一步探讨脂联素对脂肪细胞的调控机制；细胞水平：探讨脂联素对脂肪细胞内质网应激的影响；整体水平：经心外膜脂肪转染apM1基因，局部高表达脂联素，观察其抗冠状动脉粥样硬化效果。本课题应用脂联素调控心外膜脂肪的内分泌功能来抗动脉粥样硬化，可望为冠心病治疗提供新的视角和策略，作为CABG的有益补充。

中文关键词： 动脉粥样硬化;心外膜脂肪组织;脂联素;巨噬细胞

英文摘要： Coronary artery bypass graft (CABG) is a main surgical method to treatment of coronary atherosclerosis, but it can't reverse the process of coronary artery disease. Great saphenous vein used for CABG has 15% ~ 30% occlusion for 1 year, for 10 years about 50% occlusion [1, 2]. How to treat stenosis &lt; 50% or coronary diameter &lt; 1 mm and intramyocardial coronary atherosclerosis and how to prevent grafts restenosis are still a problem of surgical treatment. Epicardial fat is thought to have endocrine function, and Direct connect the coronary artery without ascia, the secretion of cytokines influence the occurrence of coronary heart disease. Our study found that patients with coronary artery disease epicardial fat tissue （EAT) macrophages infiltrating CD68 + increased, cells that secrete factors APN (adiponectin) reduce , IL-6, TNF alpha,IL-1βTLR4 secretion increased close relations with coronary heart disease; APN can restrain mononuclear cells IL-6 and TNF alpha secretion and monocytes surface TLR4 expression, may has the protection through inhibited macrophages mediated inflammation. And we also have reseached on the relation between the new discovery adipokine chemerin and atherosclerosis.

英文关键词： atherosclerosis;epicardial fat tissue;adiponectin ;macrophages