ASAP1基于YTHDF2 m6A 甲基化修饰介导巨噬细胞自噬调控AS作用和机制的研究

动脉粥样硬化性血管疾病(ASVD)是一种慢性疾病，病程时间长，同时可导致急性临床事件，探究动脉粥样硬化的发病机理和进展过程一直是本领域研究的重点和难点问题。针对本项目，我们的初步研究表明：ASAP1在动脉粥样硬化模型中表达显著增高，ASAP1是YTHDF2的直接靶点，抑制YTHDF2能够通过缩短ASAP1 mRNA半衰期，改善巨噬细胞自噬功能，从而调控动脉粥样硬化。在已有的大量前期研究基础上，本项目采用ApoE-/-敲除小鼠模型，联合细胞水平实验，应用分子生物学和生物信息学等技术，深入探究ASAP1基于YTHDF2 m6A 甲基化修饰介导巨噬细胞自噬在动脉粥样硬化中的作用，为动脉粥样硬化的发病机制提供了新的理论基础，也为动脉粥样硬化型心脑血管疾病的防治提供了新的思路和靶点。

Atherosclerotic vascular disease (ASVD) is a chronic process, with a progressive course over many years, but it can cause acute clinical events, Exploring the pathogenesis and progression of atherosclerosis are still difficult points in this field.For this project, our preliminary research shows that: ASAP1 expression is significantly increased in atherosclerosis. Moreover, we found that ASAP1 was the direct target of YTHDF2. Knockout of YTHDF2 enhances autophagy function by inhibiting ASAP1 mRNA decay in macrophage.On the basis of a large number of previous studies, we will generate ApoE-/- mice models, and combine with cell-level experiments. Molecular biological and bioinformatic techniques would be used to further explore YTHDF2 regulates the m6A modification of ASAP1 in the study of atherosclerosis caused by macrophage autophgy for providing a potential intervention target in coronary heart disease. This study will also provide new ideas and drug targets for atherosclerotic related diseases.