动脉粥样硬化是一种危害严重的慢性炎症疾病，其发生的关键步骤为脂蛋白在内皮下沉积，募集单核细胞分化为巨噬细胞，进而摄取脂蛋白转变为泡沫细胞、在动脉壁积累并分泌促炎因子，引发炎症反应。巨噬细胞在动脉粥样硬化发生过程的各个阶段都具有非常重要的作用，其增殖、迁移及极化都会影响斑块的发展，但其中的分子机制及调控分子还不完全清楚。我们近期发现：CKIP-1蛋白在动脉粥样硬化斑块中高表达，CKIP-1敲除小鼠来源的巨噬细胞体外形成泡沫细胞的能力增强；CKIP-1可以调控巨噬细胞的增殖、迁移。本项目拟在此基础上，在分子、细胞、动物模型、临床样本等多个层面，系统地研究CKIP-1作为巨噬细胞增殖及极化功能调控的关键因子、在动脉粥样硬化发生过程中的功能及调控机制。研究结果将为认识动脉粥样硬化发生过程中巨噬细胞的调控机制、阐明CKIP-1这一重要蛋白与心血管疾病的新关联提供新的科学依据。

Atherosclerosis is a chronic inflammatory disease.In atherosclerosis, the key initiating step is that the subendothelial accumulation of apolipoprotein B-containing lipoproteins leads to the recruitmet of monocytes, the cells of the immune system that give rise to macrophages. Macrophages derived from these recruited monocytes ingest the accumulated normal and modified lipoproteins, which transfrom them into the cholesterol-laden foam cells, triggering a series of inflammatory response. There is a growing understanding that macrophages play a very important role in the development of atherosclerosis.The proliferation，migration and polarization of macrophages influence plaque fate. Our recent results show that CKIP-1 was highly expressed in atherosclerotic lesions; the deficiency of CKIP-1 in mice macrophages enhanced foam cell formation in vitro; CKIP-1 regulated the proliferation and migration of macrophages. In this project, we plan to explore the function and molecular mechanism of CKIP-1 as a key regulator of macrophage proliferation and polarization in the development of atherosclerosis in cultured cells, animal models and clinical cases. The project will provide new insights to macrophage function and regulation in atherosclerosis as well as the novel role of CKIP-1 in the development of cardiovascular disease.