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Cited by 18MicroRNA in disease regulationCholesterol and Lipid MetabolismAtherosclerosis and Cardiovascular Diseases

The elevation of miR-185-5p alleviates high-fat diet-induced atherosclerosis and lipid accumulation in vivo and in vitro via SREBP2 activation

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Tan, Wenyun, Wang, Gang, Liu, Gang, You, Daofeng, Wei, Mei, Jin, Xiaojing, Zhao, Wei, Zheng, Mingqi·2022·Aging
DOI 10.18632/aging.203896PMC PMC8908921
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Abstract

Objective: SREBP2, a member of the SREBP family, is a primary regulator of lipid metabolism. In recent years, an increasing number of studies have suggested that miRNAs regulate lipid metabolism-related genes. It was speculated in this study that miRNAs may be implicated in the regulation of lipid accumulation in macrophages by SREBP2 protein. Methods and results: GSE34812, GSE132651 and GSE28829 datasets comprised of atherosclerosis samples were downloaded to explore the gene expression profiles related to the miRNAs and SREBP2, and miR-185-5p was predicted to be a target of SREBP2. The GO annotations and KEGG pathway analysis were adopted for functional classification of differentially expressed genes, and lipid metabolic process was an enriched pathway in atherosclerosis. Besides, the effects of SREBP2 on increasing lipid accumulation were investigated in vivo using miR-185-5p mimic/apoE−/− mice and miR-185-5p NC/apoE−/− mice. All mice fed with a HFD suffered from atherosclerosis. Moreover, the effects of miR-185-5p on atherosclerotic plaque formation in mice were analyzed. An in vitro assay was also performed to determine the effect of miR-185-5p on ox-LDL-stimulated RAW 264.7 macrophages. Finally, miR-185-5p mimic was transfected into cultured macrophages. The results showed that the miR-185-5p elevation might regulate lipid accumulation in mice by targeting SREBP2. Furthermore, miR-185-5p mimic repressed the activation of SREBP1, SREBP2, LDLR, SCD-1, HMGCR as well as NLRP3, IL-1β, TNF-α in HFD fed mice or ox-LDL-stimulated macrophages. Conclusions: our study demonstrated that miR-185-5p effectively alleviates atherosclerosis and lipid accumulation by regulating the miR-185-5p/SREBP2 axis.

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Cited by

Sorted by citations

Authors
Tan, W., Wang, G., Liu, G., You, D., Wei, M., Jin, X., Zhao, W., & Zheng, M.
Affiliations
  • Hebei Medical University (CN)
  • Department of Cardiology, 980 Hospital of PLA Joint Logistics Support Forces, Shijiazhuang, Hebei, China
Corresponding author
Zheng, Mingqi
ORCID
Venue
Aging
Publisher
Impact Journals, LLC
Published
2022-02-16
Volume
14
Issue
4
Pages
1729-1742
ISSN
1945-4589 (ISSN-L)
DOI
10.18632/aging.203896
PMC
PMC8908921
OpenAlex
W4213347711
Cited by
18
References
0
Citations by year
2026: 5 · 2025: 5 · 2024: 6 · 2022: 2
FWCI
1.37
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Aging (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Health Commission of Hebei Province
  • Natural Science Foundation of Hebei Province (H2020206420, 20191210, 19277757D)
  • Horizon 2020 Framework Programme
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
Keywords
miR-185-5p, SREBP2, atherosclerosis, lipid accumulation, macrophages, high-fat diet, oxidized LDL, lipid metabolism, SREBP1, LDL receptor, stearoyl-CoA desaturase 1, HMGCR, NLRP3 inflammasome, IL-1β, TNF-α, atherosclerotic plaque, microRNA regulation
MeSH terms
Animals, Apolipoproteins E, Signal Transduction, MicroRNAs, Atherosclerosis, Mice, Diet, High-Fat

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