Dicer in Macrophages Prevents Atherosclerosis by Promoting Mitochondrial Oxidative Metabolism

Circulation
Yuanyuan WeiAndreas Schober

Abstract

Alternative macrophage activation, which relies on mitochondrial oxidative metabolism, plays a central role in the resolution of inflammation and prevents atherosclerosis. Moreover, macrophages handle large amounts of cholesterol and triglycerides derived from the engulfed modified lipoproteins during atherosclerosis. Although several microRNAs regulate macrophage polarization, the role of the microRNA-generating enzyme Dicer in macrophage activation during atherosclerosis is unknown. To evaluate the role of Dicer in atherosclerosis, Apoe-/- mice with or without macrophage-specific Dicer deletion were fed a high-fat diet for 12 weeks. Anti-argonaute 2 RNA immunoprecipitation chip and RNA deep sequencing combined with microRNA functional screening were performed in the Dicer wild-type and knockout bone marrow-derived macrophages to identify the individual microRNAs and the mRNA targets mediating the phenotypic effects of Dicer. The role of the identified individual microRNA and its target in atherosclerosis was determined by tail vein injection of the target site blockers in atherosclerotic Apoe-/- mice. We show that Dicer deletion in macrophages accelerated atherosclerosis in mice, along with enhanced inflammatory response and ...Continue Reading

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Citations

Jun 15, 2018·International Journal of Molecular Sciences·Yuanyuan WeiAndreas Schober
Aug 8, 2019·Cardiovascular Research·Francesca FasoloJason L Johnson
Jan 31, 2020·Arteriosclerosis, Thrombosis, and Vascular Biology·Ela KarshovskaAndreas Schober
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Aug 11, 2020·International Journal of Endocrinology·Xiaohui TongTongsheng Wang
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Mar 20, 2020·International Journal of Molecular Sciences·Chary Lopez-PedreraCarlos Pérez-Sánchez
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May 1, 2020·Journal of Inflammation·Gaohai ShaoZhao Yang
Apr 3, 2020·International Journal of Molecular Sciences·Yunhui Jia, Yuanyuan Wei
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