microRNA-212 promotes lipid accumulation and attenuates cholesterol efflux in THP-1 human macrophages by targeting SIRT1
| Autor: | Honghui Zeng, Hui Gong, Haiwei Miao |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Apolipoprotein B THP-1 Cells Hypercholesterolemia Diet High-Fat 03 medical and health sciences chemistry.chemical_compound Mice Downregulation and upregulation Sirtuin 1 Genetics Macrophage Animals Humans Foam cell Mice Knockout biology Apolipoprotein A-I Cholesterol General Medicine Atherosclerosis Lipid Metabolism Cell biology Lipoproteins LDL MicroRNAs 030104 developmental biology chemistry ABCA1 biology.protein lipids (amino acids peptides and proteins) Lipoprotein ATP Binding Cassette Transporter 1 Foam Cells |
| Zdroj: | Gene. 643 |
| ISSN: | 1879-0038 |
| Popis: | Macrophage foam cell formation is a key initiating event in the pathogenesis of atherosclerosis. This work was conducted to determine the role of microRNA (miR)-212 in the transformation of foam cells from macrophages. We examined the expression of miR-212 in atherosclerotic lesions in an apoE-deficient (apoE-/-) mouse model. The effects of miR-212 overexpression and knockdown on lipid accumulation and cholesterol homeostasis in THP-1 macrophages after exposure to oxidized low-density lipoprotein (oxLDL). The mechanism underlying the activity of miR-212 was explored. It was found that miR-212 was downregulated in atherosclerotic lesions and macrophages from apoE-/- mice fed high-fat diet, compared to the equivalents from apoE-/- mice fed standard diet. Overexpression of miR-212 promoted lipid accumulation in oxLDL-treated THP-1 macrophages, whereas miR-212 depletion exerted an opposite effect. Macrophage cholesterol efflux to apolipoprotein A-I was significantly reduced by miR-212, which was accompanied by reduced ABCA1 expression. Mechanistically, miR-212 targeted sirtuin 1 (SIRT1) to repress the expression of ABCA1 in THP-1 macrophages. Rescue experiments confirmed that co-expression of SIRT1 attenuated lipid accumulation and restored cholesterol efflux in miR-212-overexpressing THP-1 macrophages. Collectively, miR-212 facilitates macrophage foam cell formation and suppresses ABCA1-dependent cholesterol efflux through downregulation of SIRT1. Targeting miR-212 may provide a potential therapeutic strategy for atherosclerosis. |
| Databáze: | OpenAIRE |
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