动脉粥样硬化是众多心血管疾病发生的主要病理基础，与冠心病、心肌梗塞等发生发展有密切的关系。巨噬细胞在动脉粥样硬化的各个阶段都发挥着重要的作用，能在不同阶段呈现不同的表型发挥不同的功能，而其中的调节机制尚不完全清楚。我们前期预实验发现巨噬细胞特异性敲除MKL1小鼠相比对照鼠，能明显改善LPS及盲肠结扎刺伤诱导的脓血症。此外，敲除或抑制巨噬细胞中的MKL1，对oxLDL诱导的泡沫细胞形成有明显的改善，对其机制初探发现MKL1能与SRF、Brg1协同调控清道夫受体CD36表达。这些结果提示MKL1在巨噬细胞中是一个重要的调节因子。本项目提出科学假说：MKL1通过与SRF、Brg1形成复合物，调控巨噬细胞中相关基因转录，从而影响巨噬细胞泡沫化、炎症反应、增殖以及迁移等表型，介导动脉粥样硬化的发生发展。我们的研究将为动脉粥样硬化的防治提供新的靶标，并为后续筛选活性成分提供理论依据。

Atherosclerosis is the major pathological basis for many cardiovascular diseases, which has close relationship with the occurrence and development of coronary heart disease, myocardial infarction. Macrophages play important roles in all stages of atherosclerosis. The phenotype of macrophages lilely changes during the different stages and has different function in atherosclerosis. However, the underlying regulatory mechanisms of which are not yet fully understood. Our previous study showed that macrophages defciency MKL1 significantly protected LPS injection and cecal ligation puncture induced sepsis. Further, we found that knocking down or inhibiting MKL1 in macrophages specifically decreased oxLDL-induced foam cell formation. The mechanism was studied and revealed that MKL1 could synergistically regulate the expression of CD36 with SRF and Brg1. These results suggest that MKL1 is an important regulator in macrophages. This project proposes a hypothesis that MKL1 regulates the transcription of related genes in macrophages by complexing with SRF and Brg1, thereby affecting foam formation, inflammatory response, cell proliferation, and migration in macrophages, mediating the development and progression of atherosclerosis. Our research will provide novel targets for therapeutic intervention of atherogenesis. Furthermore, our study will provide theoretical basis for screening active compound to intervene and treat atherosclerosis.