期刊
CIRCULATION JOURNAL
卷 82, 期 1, 页码 28-+出版社
JAPANESE CIRCULATION SOC
DOI: 10.1253/circj.CJ-16-1165
关键词
Atherosclerosis; Histone deacetylase 9 (HDAC9); Inflammation; Lipoprotein lipase (LPL); MicroRNA-182
资金
- National Natural Sciences Foundation of China [81270269, 81570408, 81370377, 81300224]
- Aid Program for Science and Technology Department of Hunan Province [2015JC3082, 2015JC3083, 2015JJ2120]
- Construct Program of the Key Discipline in Hunan Province
- Hunan Provincial Natural Science Foundation of China [2017JJ2234]
- Hunan Province Graduate Student Scientific Research Innovation Project [2014SCX02, 2015XCX03]
- Graduate Student Innovation Project of Cooperative Innovation Center for Molecular Target New Drug [0223-0002-D0033, 0223-0002-D0027]
- University of South China
- College Students' Innovative Project [201510555007]
- University of South China Innovation Foundation for Postgraduate [2017XCX03]
Background: Lipoprotein lipase (LPL) expressed in macrophages plays an important role in promoting the development of atherosclerosis or atherogenesis. MicroRNA-182 (miR-182) is involved in the regulation of lipid metabolism and inflammation. However, it remains unclear how miR-182 regulates LPL and atherogenesis. Methods and Results: Using bioinformatics analyses and a dual-luciferase reporter assay, we identified histone deacetylase 9 (HDAC9) as a target gene of miR-182. Moreover, miR-182 upregulated LPL expression by directly targeting HDAC9 in THP-1 macrophages. Hematoxylin-eosin (H&E), Oil Red O and Masson's trichrome staining showed that apolipoprotein E (ApoE)-knockout (KO) mice treated with miR-182 exhibited more severe atherosclerotic plaques. Treatment with miR-182 increased CD68 and LPL expression in atherosclerotic lesions in ApoE-KO mice, as indicated by double immunofluorescence staining in the aortic sinus. Increased miR-182-induced increases in LPL expression in ApoE-KO mice was confirmed by real-time quantitative polymerase chain reaction and western blotting analyses. Treatment with miR-182 also increased plasma concentrations of proinflammatory cytokines and lipids in ApoE-KO mice. Conclusions: The results of the present study suggest that miR-182 upregulates LPL expression, promotes lipid accumulation in atherosclerotic lesions, and increases proinflammatory cytokine secretion, likely through targeting HDAC9, leading to an acceleration of atherogenesis in ApoE-KO mice.
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