Lipid deposition in macrophages plays an important role in atherosclerosis. The WNT1‐inducible signalling pathway protein 1(WISP1) can promote proliferation and migration of smooth muscle cells. Its expression is up‐regulated in obesity, which is associated with atherosclerosis, but the effect of WISP1 on atherosclerosis remains unclear. Thus, the objective of our study was to elucidate the role of WISP and its mechanism of action in atherosclerosis via in vivo and in vitro experiments. In our experiment, ApoE‐/‐ mice were divided into 5 groups: control, high‐fat diet (HFD), null lentivirus (HFD + NC), lentivirus WISP1 (HFD + IvWISP1) and WISP1‐shRNA (HFD + shWISP1). Oil Red O staining, immunofluorescence and immunohistochemistry of the aortic sinuses were conducted. Macrophages (RAW264.7 cell lines and peritoneal macrophages) were stimulated with 50 μg/mL oxidized low‐density lipoprotein (ox‐LDL); then, the reactive oxygen species (ROS) level was measured. Oil Red O staining and Dil‐ox‐LDL (ox‐LDL with Dil dye) uptake measurements were used to test lipid deposition of peritoneal macrophages. WISP1, CD36, SR‐A and PPARγ expression levels were measured via Western blotting and ELISA. The results showed that HFD mice had increased WISP1, CD36 and SR‐A levels. The plaque lesion area increased when WISP1 was down‐regulated, and lipid uptake and foam cell formation were inhibited when WISP1 was up‐regulated. Treatment of RAW264.7 cell lines with ox‐LDL increased WISP1 expression via activation of the Wnt5a/β‐catenin pathway, whereas ROS inhibition reduced WISP1 expression. Moreover, WISP1 down‐regulated CD36 and SR‐A expression, and Oil Red O staining and Dil‐ox‐LDL uptake measurement showed that WISP1 down‐regulated lipid deposition in macrophages. These results clearly demonstrate that WISP1 is activated by ox‐LDL at high ROS levels and can alleviate lipid deposition in atherosclerosis through the PPARγ/CD36 pathway.

中文翻译：

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WISP1通过动脉粥样硬化斑块形成中的PPARγ/ CD36途径减轻巨噬细胞中的脂质沉积。

巨噬细胞中的脂质沉积在动脉粥样硬化中起重要作用。WNT1诱导信号通路蛋白1（WISP1）可以促进平滑肌细胞的增殖和迁移。在与动脉粥样硬化相关的肥胖症中，其表达上调，但WISP1对动脉粥样硬化的作用尚不清楚。因此，我们研究的目的是通过体内和体外实验阐明WISP的作用及其在动脉粥样硬化中的作用机理。在我们的实验中，ApoE-/-小鼠分为5组：对照组，高脂饮食（HFD），无效慢病毒（HFD + NC），慢病毒WISP1（HFD + IvWISP1）和WISP1-shRNA（HFD + shWISP1）。进行了油红O染色，主动脉窦的免疫荧光和免疫组化分析。巨噬细胞（RAW264。用50μg/ mL氧化的低密度脂蛋白（ox-LDL）刺激7个细胞系和腹膜巨噬细胞）; 然后，测量活性氧（ROS）水平。油红O染色和Dil-ox-LDL（含Dil染料的ox-LDL）摄取测量用于测试腹膜巨噬细胞的脂质沉积。通过Western印迹和ELISA检测WISP1，CD36，SR‐A和PPARγ的表达水平。结果显示，HFD小鼠的WISP1，CD36和SR‐A水平升高。当WISP1被下调时，斑块病变面积增加，而当WISP1被上调时，脂质摄取和泡沫细胞形成受到抑制。用ox-LDL处理RAW264.7细胞系可通过激活Wnt5a /β-catenin途径提高WISP1表达，而ROS抑制则降低WISP1表达。此外，WISP1下调了CD36和SR‐A的表达，油红O染色和Dil-ox-LDL吸收测量结果表明，WISP1下调了巨噬细胞中的脂质沉积。这些结果清楚表明，WISP1在高ROS水平下被ox-LDL激活，并可以通过PPARγ/ CD36途径减轻动脉粥样硬化中的脂质沉积。