探讨动脉粥样硬化（AS）的发生机制是当前的研究热点之一。众多研究表明，巨噬细胞脂质沉积是AS斑块形成的重要病理生理学基础，但微环境中调控巨噬细胞脂质沉积的相关机制尚未阐明。WISP1作为Wnt信号通路中的关键蛋白，在动脉粥样硬化中的作用尚未见报道。我们的前期研究发现：在ApoE-/-小鼠斑块中WISP1表达显著增加；rWISP1促进了oxLDL诱导的巨噬细胞脂质沉积；抑制WISP1后，脂质沉积减少，同时WISP1可降低PPARγ及其下游因子ABCA1和ABCG1的表达。据此，我们提出了如下科学假说：WISP1通过抑制PPARγ来降低巨噬细胞中胆固醇外流，促进脂质沉积，从而加重动脉粥样硬化的发生发展。本课题拟在此基础上，利用巨噬细胞特异性敲除WISP1小鼠，运用细胞分子生物学相关技术，深入探究WISP1在巨噬细胞介导的AS中的作用及分子机制，为AS相关疾病的防治提供新的干预靶点和实验佐证。

It has become a hot topic in cardiovascular area to explore the mechanism of the development of atherosclerosis(AS). Recent studies have found that lipid deposition in macrophage plays an important role in the pathological and physiological process of AS, while the related mechanism in regulating micro-environment of lipid deposition in macrophage is unclear. Wnt1-inducible signaling pathway protein 1(WISP1) is a key protein in the Wnt signaling pathway, but it is still not clarified about the effect of WISP1 on AS.Our previous studies demonstrated that the expression of WISP1 increases significantly in atherosclerotic plaques in ApoE-/- mouse and exogenous stimulus of rWISP1 could promote the lipid deposition in macrophage induced by oxLDL. Lipid deposition in macrophage can be reduced after inhibiting the expression of WISP1. What's more，the increase of WISP1 could decrease the expression of PPAR-γ、ABCA1 and ABCG1.Based on our preliminary research, the scientific hypothesis is proposed that WISP1 in macrophages reduces cholesterol efflux by inhibiting PPARγ and promotes lipid deposition in macrophage which will eventually aggravate the pathogenesis of atherosclerosis. We aim to investigate further mechanism of WISP1 in the development of AS through macrophage specific WISP1 knockout mice and related techniques on molecular biology，which will provide the experimental evidence and potential new treatment target for arteriosclerotic cardiovascular disease（ASCVD）.