Hypomethylation of Agtrap is associated with long-term inhibition of left ventricular hypertrophy in prehypertensive losartan-treated spontaneously hypertensive rats

  • Authors:
    • Ting‑Jun Wang
    • Gui‑Li Lian
    • Xu Lin
    • Hong‑Bin Zhong
    • Chang‑Sheng Xu
    • Hua‑Jun Wang
    • Liang‑Di Xie
  • View Affiliations

  • Published online on: December 14, 2016     https://doi.org/10.3892/mmr.2016.6040
  • Pages: 839-846
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Abstract

Prehypertensive losartan treatment may lead to long‑term inhibition of the development of left ventricular hypertrophy (LVH) in spontaneously hypertensive rats (SHRs). However, the underlying mechanism has yet to be fully elucidated. The aim of the present study was to investigate the expression of angiotensin type 1 receptor-associated protein (ATRAP/Agtrap) and methylation of the Agtrap gene in the myocardium following the withdrawal of treatment. Four‑week‑old SHRs were randomly divided into three groups, and were treated with saline, amlodipine or losartan, respectively, for 6 weeks. Wistar Kyoto rats (WKYs) were used as a control. All rats were followed up regularly until they reached the age of 32 weeks. Systolic blood pressure (SBP), left ventricular mass/body weight (LVM/BW), and cardiac fibrosis and structure were measured. The mRNA and protein expression of ATRAP in the myocardium were determined using reverse transcription‑quantitative polymerase chain reaction and western blot analysis. Methylation of the Agtrap promoter was detected by bisulfite pyrosequencing. Reduced levels of SBP, LVM/BW, cardiac fibrosis and interventricular septum thickness were determined to be maintained only in prehypertensive losartan‑treated SHRs. Whereas, an increased expression of ATRAP mRNA and protein, and hypomethylation of the Agtrap promoter in the myocardium, were demonstrated only in the losartan‑treated SHRs. In conclusion, the results of the present study suggested that the hypomethylation of Agtrap accompanying upregulation of ATRAP expression in the myocardium is associated with the long‑term inhibition of LVH in SHRs with prehypertensive losartan treatment.
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February-2017
Volume 15 Issue 2

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

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Spandidos Publications style
Wang TJ, Lian GL, Lin X, Zhong HB, Xu CS, Wang HJ and Xie LD: Hypomethylation of Agtrap is associated with long-term inhibition of left ventricular hypertrophy in prehypertensive losartan-treated spontaneously hypertensive rats. Mol Med Rep 15: 839-846, 2017
APA
Wang, T., Lian, G., Lin, X., Zhong, H., Xu, C., Wang, H., & Xie, L. (2017). Hypomethylation of Agtrap is associated with long-term inhibition of left ventricular hypertrophy in prehypertensive losartan-treated spontaneously hypertensive rats. Molecular Medicine Reports, 15, 839-846. https://doi.org/10.3892/mmr.2016.6040
MLA
Wang, T., Lian, G., Lin, X., Zhong, H., Xu, C., Wang, H., Xie, L."Hypomethylation of Agtrap is associated with long-term inhibition of left ventricular hypertrophy in prehypertensive losartan-treated spontaneously hypertensive rats". Molecular Medicine Reports 15.2 (2017): 839-846.
Chicago
Wang, T., Lian, G., Lin, X., Zhong, H., Xu, C., Wang, H., Xie, L."Hypomethylation of Agtrap is associated with long-term inhibition of left ventricular hypertrophy in prehypertensive losartan-treated spontaneously hypertensive rats". Molecular Medicine Reports 15, no. 2 (2017): 839-846. https://doi.org/10.3892/mmr.2016.6040