慢性炎症反应和巨噬细胞泡沫化是介导动脉粥样硬化（AS）发生发展的重要病理过程。表皮生长因子受体（EGFR）是目前肿瘤靶向治疗的重要靶点之一，近年来发现EGFR还可以介导一些心肾慢性疾病的发生发展。我们前期研究发现：口服EGFR抑制剂埃罗替尼在高脂饮食的ApoE-/-小鼠中显著缓解AS；在体外，埃罗替尼能够明显抑制oxLDL引起的巨噬细胞炎症反应与泡沫化。因此我们假设，EGFR可以介导高血脂诱导的炎症反应和泡沫化，可能成为AS的防治新靶点。本项目中，我们拟在细胞层面阐明高血脂元素ox-LDL和FFA激活EGFR介导炎症反应和泡沫化的上下游分子机制；动物层面利用高脂饮食的LDLR-/-小鼠进一步确证埃罗替尼对AS的防治作用；在临床层面初步探讨血液单核细胞中的EGFR表达和激活与AS的相关性。项目将阐明EGFR在AS中的作用及其介导高血脂炎症和泡沫化的分子机制，为防治AS提供新药物和新靶点。

Chronic inflammation and macrophage foam cell formation mediate development and pathological process of atherosclerosis (AS). It was reported that epidermal growth factor receptor (EGFR), a classic target for cancer therapy, can also mediated the development of some chronic benign diseases such as heart and kidney diseases in recent years. Our previous studies found that orally giving EGFR inhibitor erlotinib significantly alleviated AS development in ApoE-/- mice feed with high-fat diet; In vitro, erlotinib can significantly attenuate oxLDL-induced inflammation and macrophage foam cell formation. Therefore, we hypothesis: EGFR may mediate the inflammatory response and foam cell formation induced by high fat and may become a new target for AS prevention and treatment. In this project, we intend to elucidate the upstream and downstream molecular mechanism of activated EGFR induced by FFA and ox-LDL mediated inflammation and macrophage foam cell formation at cell level. At animal level, we will confirm the prevention and treatment role of erlotinib in high-fat diet feed LDLR-/- mice. At clinical, we will explore the relationship between AS and the expression and activation of EGFR in peripheral blood mononuclear cells. This project will elucidate the role of EGFR in the AS and the molecular mechanisms of inflammation and macrophage foam cell formation. It will provide drugs and new targets for prevention and treatment of AS.