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MicroRNA‑126 inhibits endothelial permeability and apoptosis in apolipoprotein E‑knockout mice fed a high‑fat diet

  • Authors:
    • Xiao‑Wen Cheng
    • Yu‑Feng Wan
    • Qing Zhou
    • Yuan Wang
    • Hua‑Qing Zhu

  • View Affiliations

  • Published online on: July 12, 2017     https://doi.org/10.3892/mmr.2017.6952
  • Pages: 3061-3068

  • Copyright: © Cheng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Endothelial dysfunction and apoptosis have key roles in the initiation and progression of atherosclerosis (AS). AS has been demonstrated to be associated with a high‑fat diet, which may increase endothelial permeability and apoptosis; however, the exact mechanisms underlying the development of AS remain poorly understood. MicroRNAs (miRNAs) are vital for the regulation of cardiovascular disease, and dysregulated miRNAs have been implicated in AS. The present study investigated whether miRNA (miR)‑126 regulates high‑fat diet‑induced endothelial permeability and apoptosis by targeting transforming growth factor β (TGFβ), a secreted protein that controls cellular proliferation and apoptosis. In the present study, apolipoprotein E (apoE)‑/‑ mice were fed a high‑fat diet in order to establish a model of AS. Mice were subcutaneously injected with a miR‑126 mimic, a miR‑126 antagomir or control miRNA. Reverse transcription‑quantitative polymerase chain reaction was used to assess miR‑126 expression, and a fluorometric assay was used to evaluate caspase‑3 activity. The effects of miR‑126 on the endothelial permeability of the aortic intima were also explored. Western blotting and immunohistochemical analysis were used to investigate the effects of miR‑126 on B‑cell lymphoma‑2 (Bcl‑2) and transforming growth factor (TGF) β protein expression levels. Furthermore, a luciferase assay was performed to verify whether TGFβ may be a direct target gene of miR‑126. In apolipoprotein E‑knockout mice, a high‑fat diet reduced miR‑126 expression and induced apoptosis as determined by the upregulation of caspase‑3 activity. A miR‑126 antagomir increased endothelial permeability and apoptosis in mice fed a high‑fat diet. By contrast, an miR‑126 mimic attenuated endothelial permeability and apoptosis. The reduction in miR‑126 was associated with a reduction in protein expression levels of Bcl‑2 and an increase of TGFβ in mice fed a high‑fat diet. In addition, the present study demonstrated that miR‑126 reduced TGFβ expression following binding to the 3'‑untranslated region of TGFβ mRNA. The current study demonstrated a role for miR‑126 in AS and identified TGFβ as a direct target of miR‑126. Furthermore, the present study demonstrated that miR‑126 contributed to endothelial permeability and apoptosis, and suggested that the downregulation of TGFβ may be involved in the molecular mechanisms underlying the actions of miR‑126. miR‑126 may therefore have potential as a novel therapeutic target for the treatment of AS.
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September-2017
Volume 16 Issue 3

Print ISSN: 1791-2997
Online ISSN:1791-3004

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  • Impact Factor: 3.4
  • Ranked Medicine Research and Experimental
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  • CiteScore: 7.6
  • CiteScore Rank: Q1: #82/347 Biochemistry, Genetics and Molecular Biology
  • Source Normalized Impact per Paper (SNIP): 0.647
  • SCImago Journal Rank (SJR): 0.781
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Spandidos Publications style
Cheng XW, Wan YF, Zhou Q, Wang Y and Zhu HQ: MicroRNA‑126 inhibits endothelial permeability and apoptosis in apolipoprotein E‑knockout mice fed a high‑fat diet. Mol Med Rep 16: 3061-3068, 2017.
APA
Cheng, X., Wan, Y., Zhou, Q., Wang, Y., & Zhu, H. (2017). MicroRNA‑126 inhibits endothelial permeability and apoptosis in apolipoprotein E‑knockout mice fed a high‑fat diet. Molecular Medicine Reports, 16, 3061-3068. https://doi.org/10.3892/mmr.2017.6952
MLA
Cheng, X., Wan, Y., Zhou, Q., Wang, Y., Zhu, H."MicroRNA‑126 inhibits endothelial permeability and apoptosis in apolipoprotein E‑knockout mice fed a high‑fat diet". Molecular Medicine Reports 16.3 (2017): 3061-3068.
Chicago
Cheng, X., Wan, Y., Zhou, Q., Wang, Y., Zhu, H."MicroRNA‑126 inhibits endothelial permeability and apoptosis in apolipoprotein E‑knockout mice fed a high‑fat diet". Molecular Medicine Reports 16, no. 3 (2017): 3061-3068. https://doi.org/10.3892/mmr.2017.6952