Depletion of β-arrestin-1 in macrophages enhances atherosclerosis in ApoE-/- mice

文献类型： 外文期刊

第一作者： Shao, Bo-Zong

作者： Shao, Bo-Zong;Liu, Meng-Zhen;Zhu, Dan-Ni;Yan, Hui;Ke, Ping;Han, Ting;Liu, Chong;Wei, Wei

作者机构：

关键词： beta-arrestin-1; Atherosclerosis; Autophagy; Macrophage; Inflammation

期刊名称：INTERNATIONAL IMMUNOPHARMACOLOGY （ 影响因子：5.6； 五年影响因子：5.6 ）

ISSN： 1567-5769

年卷期： 2023 年 125 卷

页码：

收录情况： SCI

摘要： Autophagy in atherosclerotic plaque macrophage contributes to the alleviation of atherosclerosis through the promotion of lipid metabolism. beta-arrestins are multifunctional proteins participating various kinds of cellular signaling pathways. Here we aimed to determine the role of beta-arrestin-1, an important member of beta-arrestin family, in atherosclerosis, and whether autophagy was involved in this process. ApoE(-/-)beta-arrestin-1(fl/fl)LysM-Cre mice were created through bone marrow transplantation for the atherosclerosis model with conditional myeloid knocking out beta-arrestin-1. Bone marrow-derived macrophages (BMDMs) were used for the in vitro studies. Oil red O staining was used to detect the lesional area. F4/80, Masson trichrome and picro-Sirius red staining were applied for the determination of plaque stability. Real-time PCR was used for the detection of levels of lipid metabolism-related receptors. Electron microscopy and tandem fluorescent mRFP-GFP-LC3 plasmid was applied to test autophagy level. We found that beta-arrestin-1 was highly increased in expression in plaque macrophage on the occurrence of atherosclerosis. Conditional myeloid knocking out beta-arrestin-1 largely promotes plaque for-mation and vulnerability. In murine macrophage with lipid loading, knocking down beta-arrestin-1 enhanced foam cell formation and levels of plasma and cellular cholesterol, while overexpressing beta-arrestin-1 led to the opposite effects. The alleviative effects induced by macrophage beta-arrestin-1 in atherosclerosis were involved in autophagy, based on the reduction of autophagy level with the knocking down of macrophage beta-arrestin-1 and administration of autophagy inhibitors which largely attenuated the decreasing effect on foam cell formation. Our results demonstrated for the first time that macrophage beta-arrestin-1 protected against atherosclerosis through the induction of autophagy.

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