血管内皮细胞(ECs)凋亡和平滑肌细胞(VSMCs)增殖共存是动脉粥样硬化(As)的基本病理特征，同型半胱氨酸(Hcy)是As的独立危险因子，但何以同条件下两类细胞增殖态变化迥异至今无解。精氨酸甲基化是基因转录调控的重要方式，且近年来发现E2F1是细胞增殖和凋亡的共同靶基因，但E2F1及其精氨酸甲基化是否参与了调控ECs凋亡和VSMCs增殖及机制尚未清楚。因此本课题拟探讨E2F1在Hcy致ECs凋亡和VSMCs增殖共存中的作用；分析E2F1精氨酸残基甲基化的变化，筛选并确定特异性精氨酸甲基转移酶(PRMTs)，重点探寻PRMT1,5竞争性修饰E2F1精氨酸R109、R111、R113甲基化修饰的潜在差异，并明确其相互作用结构域和精确位点，阐明Hcy经PRMTs调控E2F1精氨酸甲基化的机制；运用SELEX技术确定Hcy致ECs凋亡和VSMCs增殖共存的干预靶位，为As靶向治疗提供理论依据。

The coexistence of endothelial cells (ECs) apoptosis and vascular smooth muscle cells (VSMCs) proliferation is an important pathologic characteristic of atherosclerosis, and homocysteine (Hcy) is an independent risk factor for atherosclerosis, but it is remains unresolved that why the changes of two types of cells proliferous states are so different under the same condition. Arginine methylation is an important way of regulating gene transcription，and some studies have found that E2F1 is a common target gene of cell proliferation and apoptosis in recent years, but the mechanisms of E2F1 arginine methylation involved in the regulation of ECs apoptosis and VSMCs proliferation are not yet clear. Therefore, this subject intends to explore the role of E2F1 in Hcy-induced the coexistence of ECs apoptosis and VSMCs proliferation; To analyse the changes of E2F1 arginine residues methylation, screen and verify the specific arginine methyltransferase (PRMTs), the exploration of PRMT1 and PRMT5 modify adjacent three arginine residues(R109,R111,R113) of E2F1 competitively is the focus. To clarify its interaction domains and precise sites, reveal the mechanisms that Hcy regulate E2F1 arginine residues methylation by PRMTs; Using SELEX techniques to determine the intervention target of Hcy-induced the coexistence of ECs apoptosis and VSMCs proliferation. Our study will provide the theoretical basis for targeted therapy of As.