Research Paper Volume 14, Issue 4 pp 1729—1742
The elevation of miR-185-5p alleviates high-fat diet-induced atherosclerosis and lipid accumulation in vivo and in vitro via SREBP2 activation
- 1 Department of Cardiology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
- 2 Department of Cardiology, 980 Hospital of PLA Joint Logistics Support Forces, Shijiazhuang, Hebei, China
- 3 Department of Emergency, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
- 4 Department of Ultrasound, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
Received: April 11, 2021 Accepted: January 25, 2022 Published: February 16, 2022https://doi.org/10.18632/aging.203896
How to Cite
Copyright: © 2022 Tan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.
POCD: Postoperative cognitive dysfunction; IP3: Inositol 1, 4, 5-triphosphate; ER: endoplasmic reticulum; PKA: cAMP-dependent protein kinase; PKG: cGMP-dependent protein kinase; CaMKII: Ca2+ / CaM dependent protein kinase II; GEO: GENE EXPRESSION OMNIBUS; GO: gene ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; gsea: Gene Set Enrichment Analysis; H&E: Hematoxylin and eosin; CytC: Cytochrome C; MPTP: mitochondrial permeability transformation channel protein; GRP78: glucose regulatory protein 78; GRP94: glucose regulatory protein 94; CHOP: C/EBP Homology protein; XBPl: X box binding protein 1.