10/11易位家族蛋白2和羟甲基化修饰在动脉粥样硬化中的作用及其机制

The role and mechanism of ten-eleven translocation 2 and hydroxymethylation in atherosclerosis

动脉粥样硬化(As)是心脑血管疾病的重要病理基础。近年来,许多研究表明表观遗传机制在As的调控中也起着重要作用。被称为DNA第6种碱基的5-羟甲基胞嘧啶(5hmC)是染色体10/11易位家族蛋白(TET)介导DNA去甲基化产生的一种重要表观遗传修饰,参与多种生物学过程。最近研究表明,TET2及其介导的羟甲基化修饰不仅参与血管平滑肌细胞表型转化调控,还与内皮功能、炎症免疫反应等As的关键因素密切相关。在As斑块中也检测到TET2和5hmC明显缺失,缺失水平与损伤程度呈正相关。TET2和羟甲基化修饰可能在As的病理过程中发挥重要保护作用。本文将介绍TET2的结构及其功能、5hmC的研究概况及检测技术突破,重点阐述TET2及其介导的羟甲基化修饰在As中的作用及其机制,为As的有效防治提供新思路和新靶点。

Atherosclerosis (As) is an important pathological basis for cardio-cerebrovascular diseases.In recent years,many studies have shown that epigenetic mechanisms also play an important role in the regulation of As.5-hydroxymethyl cytosine (5hmC),known as the sixth base of human DNA,is an important epigenetic modification derived from the demethylation process of DNA mediated by the ten-eleven translocation (TET) protein family,and has been known to involve in various biological processes.Recent studies have shown that TET2 and its mediated hydroxymethylation are not only involved in the regulation of phenotypic transformation of vascular smooth muscle cells,but also closely related to the key factors of As such as endothelial function and inflammatory immune response.It is also found that TET2 and 5hmC are markedly absent in As plaque,and the level of deletion is positively correlated with the degree of injury.TET2 and hydroxymethylation may play an important protective role in the pathological process of As.This review will introduce the structure and function of TET2,the research overview of 5hmC and the breakthrough in detection techniques.It will focus on the role and mechanism of TET2 and its mediated hydroxymethylation modification in As,and provide new ideas and targets for the effective prevention and treatment of As.