期刊
CIRCULATION JOURNAL
卷 82, 期 11, 页码 2861-+出版社
JAPANESE CIRCULATION SOC
DOI: 10.1253/circj.CJ-18-0410
关键词
Atherosclerosis; DNA methyltransferase 1 (DNMT1); Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1); Lipoprotein lipase (LPL); MicroRNA-377
资金
- National Natural Sciences Foundation of China [81570408]
- University of South China Innovation Foundation for Postgraduate [2017XCX03]
- construct program of the key discipline in Hunan Province, China (Basic Medicine Sciences in University of South China, Xiangjiaofa) [[2011]76]
Background: Lipoprotein lipase (LPL) plays an important role in triglyceride metabolism. It is translocated across endothelial cells to reach the luminal surface of capillaries by glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 (GPIHBP1), where it hydrolyzes triglycerides in lipoproteins. MicroRNA 377 (miR-377) is highly associated with lipid levels. However, how miR-377 regulates triglyceride metabolism and whether it is involved in the development of atherosclerosis remain largely unexplored. Methods and Results: The clinical examination displayed that miR-377 expression was markedly lower in plasma from patients with hypertriglyceridemia compared with non-hypertriglyceridemic subjects. Bioinformatics analyses and a luciferase reporter assay showed that DNA methyltransferase 1 (DNMT1) was a target gene of miR-377. Moreover, miR-377 increased LPL binding to GPIHBP1 by directly targeting DNMT1 in human umbilical vein endothelial cells (HUVECs) and apolipoprotein E (ApoE)-knockout (KO) mice aorta endothelial cells (MAECs). In vivo, hematoxylin-eosin (H&E), Oil Red O and Masson's trichrome staining showed that ApoE-KO mice treated with miR-377 developed less atherosclerotic plaques, accompanied by reduced plasma triglyceride levels. Conclusions: It is concluded that miR-377 upregulates GPIHBP1 expression, increases the LPL binding to GPIHBP1, and reduces plasma triglyceride levels, likely through targeting DNMT1, inhibiting atherosclerosis in ApoE-KO mice.
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