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Updated: Feb 23, 2026
Quantification of Atherosclerosis in Mice
Published on: June 12, 2019
MicroRNA-182 Promotes Lipoprotein Lipase Expression and Atherogenesisby Targeting Histone Deacetylase 9 in
Hai-Peng Cheng1, Duo Gong1, Zhen-Wang Zhao1
1Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China.
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 targetingHDAC9in 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 targetingHDAC9, leading to an acceleration of atherogenesis in ApoE-KO mice.
Insights
MicroRNA-182 (miR-182) accelerates atherosclerosis by increasing lipoprotein lipase (LPL) via targeting histone deacetylase 9 (HDAC9). This leads to more severe plaques and inflammation in mice.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Atherosclerosis Research
Background:
- Lipoprotein lipase (LPL) in macrophages is crucial for atherogenesis.
- MicroRNA-182 (miR-182) influences lipid metabolism and inflammation.
- The regulatory role of miR-182 on LPL and atherogenesis is not well understood.
Purpose of the Study:
- To investigate the mechanism by which miR-182 regulates LPL and atherogenesis.
- To identify the direct target of miR-182 involved in this process.
Main Methods:
- Bioinformatics analysis and dual-luciferase reporter assay to identify miR-182 targets.
- In vitro studies using THP-1 macrophages.
- In vivo studies using apolipoprotein E-knockout (ApoE-KO) mice.
- Histological analyses (H&E, Oil Red O, Masson's trichrome) and molecular techniques (qPCR, Western blotting, immunofluorescence).
Main Results:
- Histone deacetylase 9 (HDAC9) was identified as a direct target of miR-182.
- miR-182 upregulated LPL expression by targeting HDAC9 in macrophages.
- miR-182 treatment worsened atherosclerotic plaques in ApoE-KO mice.
- Increased LPL and CD68 expression, elevated pro-inflammatory cytokines, and lipids were observed in miR-182 treated ApoE-KO mice.
Conclusions:
- miR-182 accelerates atherogenesis in ApoE-KO mice.
- This acceleration is mediated by miR-182-induced upregulation of LPL expression through targeting HDAC9.
- The findings highlight miR-182 as a potential therapeutic target in atherosclerosis.
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