MicroRNA-377 Inhibits Atherosclerosis by Regulating Triglyceride Metabolism Through the DNA Methyltransferase 1 in Apolipoprotein E-Knockout Mice

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  • Chen Ling-Yan
    Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China
  • Xia Xiao-Dan
    Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China
  • Zhao Zhen-Wang
    Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China
  • Gong Duo
    Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China
  • Ma Xiao-Feng
    Department of Internal Medicine-Cardiovascular, Nanhua Hospital, University of South China
  • Yu Xiao-Hua
    Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China
  • Zhang Qiang
    Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China
  • Wang Si-Qi
    Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China
  • Dai Xiao-Yan
    Key Laboratory of Molecular Target & Clinical Pharmacology, School of Pharmaceutical Sciences & the Fifth Affiliated Hospital, Guangzhou, Medical University
  • Zheng Xi-Long
    Department of Biochemistry and Molecular Biology, Libin Cardiovascular Institute of Alberta, Cumming School of Medicine, University of Calgary, Health Sciences Center
  • Zhang Da-Wei
    Department of Pediatrics and Group on the Molecular and Cell Biology of Lipids, University of Alberta
  • Yin Wei-Dong
    Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China
  • Tang Chao-Ke
    Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China

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<p>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. </p><p>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. </p><p>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. </p>

収録刊行物

  • Circulation Journal

    Circulation Journal 82 (11), 2861-2871, 2018-10-25

    一般社団法人 日本循環器学会

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