以ABCA1为靶点防治动脉粥样硬化  

ATP-Binding Cassette Transporter A1(ABCA1) as Novel Target for Treatment of Atherosclerosis

作　　者：唐朝克[1] 

机构地区：[1]南华大学心血管病研究所湖南省动脉硬化学重点实验室,湖南省衡阳市421001

出　　处：《中国动脉硬化杂志》2011年第11期879-884,共6页Chinese Journal of Arteriosclerosis

基　　金：国家自然科学基金资助项目(81170278;81070220);湖南省自然科学衡阳联合基金资助项目(10JJ9019)

摘　　要：动脉粥样硬化(atherosclerosis,As)是一个多因素参与的复杂疾病,其中血管壁胆固醇蓄积和炎症反应是其发生发展的两个关键环节,而两者又相互促进。三磷酸腺苷结合盒转运体A1(ATP binding cassette transporterA1,ABCA1)是一种膜整合蛋白,通过与载脂蛋白AⅠ(apoAⅠ)结合,促进细胞内胆固醇流出并抑制血管壁炎症反应。人类ABCA1基因突变导致血浆高密度脂蛋白(HDL)水平降低,并增加心血管疾病的风险。ABCA1基因敲除动物不仅表现出低的血浆HDL水平,还表现出胰腺β细胞功能紊乱、体内促炎状态和As斑块的形成。多种促As的炎症因子和代谢产物可能通过下调ABCA1的表达,从而促进As相关心血管疾病的发展。因此,ABCA1有望成为心血管疾病和糖尿病新的治疗靶标和研究方向。Atherosclerosis（As） is a complex process where both of cholesterol accumulation and inflammation in vessel wall play crucial roles in its development.ATP-binding cassette transporter A1（ABCA1） is an integral cell membrane protein that exports cholesterol from cells and suppresses vascular inflammation via binding of the apolipoprotein AⅠ（apoAⅠ）.ABCA1 mutations in human can reduce plasma HDL levels and increase the risk for cardiovascular disease.Genetic knockout of ABCA1 in animal not only affect plasma HDL levels but also impair pancreatic β cell function,inflammation and promoting the progress of atherosclerosis.Inflammatory cytokines and metabolites inhibit ABCA1 protein and decrease cholesterol export from macrophages,raising the possibility that an impaired ABCA1 pathway contributes to the enhanced atherogenesis associated with common inflammatory and metabolic disorders.The ABCA1 has therefore become a promising new therapeutic target for treating atherosclerosis.

关 键 词：三磷酸腺苷结合盒转运体A1 动脉粥样硬化 胆固醇逆向转运 炎症 

分 类 号：R363[医药卫生—病理学]