Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
ISSN-L : 1346-9843
Metabolic Disorder
MicroRNA-377 Inhibits Atherosclerosis by Regulating Triglyceride Metabolism Through the DNA Methyltransferase 1 in Apolipoprotein E-Knockout Mice
Ling-Yan ChenXiao-Dan XiaZhen-Wang ZhaoDuo GongXiao-Feng MaXiao-Hua YuQiang ZhangSi-Qi WangXiao-Yan DaiXi-Long ZhengDa-Wei ZhangWei-Dong YinChao-Ke Tang
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2018 Volume 82 Issue 11 Pages 2861-2871

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Abstract

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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© 2018 THE JAPANESE CIRCULATION SOCIETY
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