中等强度有氧运动防治动脉粥样硬化（AS）的机制复杂且至今未明，表观遗传修饰是连接生活方式与遗传因素的重要桥梁，然而中等强度有氧运动通过RNA甲基化抗AS的机制尚不清楚。申请人前期研究发现中等强度有氧运动明显降低AS患者外周血单核细胞m6A水平及m6A甲基转移酶Mettl14水平，体外干扰Mettl14诱导巨噬细胞向M2型极化，推测出Mettl14是中等强度有氧运动通过RNA甲基化抗AS的关键分子。应用生物信息学方法预测出Mettl14通过STAT3调控IL-10。因此，申请人首次提出中等强度有氧运动通过Mettl14/STAT3/IL-10通路诱导巨噬细胞向M2型极化从而抗AS的科学假设。本项目拟从分子、细胞、转基因模式动物等多层次阐明中等强度有氧运动通过RNA甲基转移酶Mettl14抗AS的具体分子机制，完善中等强度有氧运动抗AS的RNA甲基化调控机制，为临床预防和治疗AS提供新的思路。

The mechanism of moderate-intensity aerobic exercise in preventing and treating atherosclerosis (AS) is complex and unclear. Epigenetic modification is an important bridge connecting lifestyle and genetic factors. However, the mechanism of moderate-intensity aerobic exercise against AS through RNA methylation is unclear. Our previous study found that moderate-intensity aerobic exercise significantly reduced the level of m6A and m6A methyltransferase Mettl14 in peripheral blood mononuclear cells of patients with AS, while siMettl14 induced macrophages to M2 polarization in vitro. We speculate that Mettl14 is a key molecule for moderate-intensity aerobic exercise to resist AS through RNA methylation. We predict that Mettl14 regulates IL-10 via STAT3 through bioinformatics. Therefore, for the first time, we propose the scientific hypothesis that medium-intensity aerobic exercise induces macrophages to M2 type polarization through the Mettl14/STAT3/IL-10 pathway to resist AS. This project intends to elucidate the specific molecular mechanism of moderate-intensity aerobic exercise through RNA methyltransferase Mettl14 anti-AS from multiple levels of molecules, cells, and transgenic mice. This project improves the RNA methylation mechanism of anti-AS for moderate-intensity aerobic exercise, and provides new ideas for clinical prevention and treatment of AS.