胆固醇的合成、分解及逆向转运与动脉粥样硬化密切相关.叉头转录因子的0亚型3(fork head box 03,Fox03)/去乙酰化酶6复合物(Sirt6 complex)、3β-脱氢胆固醇-△24还原酶(3β-hydroxysterol △(24)-reductase,DHCR24, Seladin-1)和死亡结构域相关蛋白(death domain associated protein,Daxx)可以通过调控核转录激活因子,甾醇调节元件结合蛋白(sterol regulatory element-binding proteins,SREBPs)的表达和活化来调节胆固醇合成限速酶[如3-羟基3-甲基戊二酰辅酶A还原酶(3-hydroxy-3-methylglutaryl-coenzyme A reductase,HMGCR)]等的转录,最终调控胆固醇的合成;外周组织的胆固醇逆向转运至肝脏后在细胞色素P450超家族(cytochrome P450 proteins,CYP)的作用下分解成胆汁酸或类固醇激素.胆固醇的分解代谢则受精脒,精胺-N1-乙酰基转移酶、Prospero相关同源蛋白1和Daxx等的严密调控;胆固醇逆向转运是防止动脉粥样硬化斑块和坏死中心形成的关键因素.肿瘤坏死因子α和红细胞很可能在巨噬细胞介导的胆固醇逆向转运中起着非常重要的作用.
胆固醇、合成、分解、逆向转运、动脉粥样硬化
34
R36;R58
国家自然科学基金30971267,31371161,81173047;湖南省高校创新平台开放基金项目12K096;湖南省自然科学基金14JJ1024. This work was supported by the National Natural Science Foundation of China30971267,31371161,81173047;the Platform Open Innovation Fund Project in Hunan Province Colleges and Universities12K096;the Natural Science Foundation of Hunan Province14JJ1024;P.R.China