Open Access

Spironolactone alleviates myocardial fibrosis via inhibition of Ets‑1 in mice with experimental autoimmune myocarditis

  • Authors:
    • Wen-Ke Wang
    • Ben Wang
    • Xue-Hu Cao
    • Yu-Sheng Liu
  • View Affiliations

  • Published online on: April 5, 2022     https://doi.org/10.3892/etm.2022.11296
  • Article Number: 369
  • Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Spironolactone improves cardiac structure, function and prognosis in patients with heart failure and delays the progression of cardiac fibrosis. However, the exact underlying mechanism of this process remains to be elucidated. The present study therefore aimed to explore the protective effect and underlying mechanism of the aldosterone receptor antagonist, spironolactone, on myocardial fibrosis in mice with experimental autoimmune myocarditis (EAM). The EAM model was induced in BALB/c mice via immunization with murine cardiac α‑myosin heavy chain sequence polypeptides. The cardiac function of the mice was assessed using echocardiography and the levels of inflammatory cytokines were quantified using ELISA. E26 transformation‑specific sequence‑1 (Ets‑1) expression was knocked down using lentivirus‑mediated small interference RNA. Total collagen deposition was assessed using Masson's trichrome and Ets‑1, TGF‑β1, Smad2/3, collagen I and III protein expression levels were detected using immunohistochemistry and western blotting. MMP‑2 and MMP‑9 mRNA expression levels and activity was determined using reverse transcription‑quantitative PCR and gelatin zymography, respectively. The results of the present study demonstrated that spironolactone significantly improved myocardium hypertrophy, diastolic cardiac function and decreased myocardial inflammation and collagen deposition induced by EAM. Spironolactone treatment significantly inhibited Ets‑1 and smad2/3 phosphorylation. In addition, inhibition of Ets‑1 reduced the expression and activity of MMP‑2 and MMP‑9 and decreased cardiac fibrosis in EAM mice. The results indicated that the improvement of myocardial fibrosis by spironolactone may be associated with the TGF‑β1/Smad‑2/3/Ets‑1 signaling pathway in EAM mice.
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June-2022
Volume 23 Issue 6

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Wang W, Wang B, Cao X and Liu Y: Spironolactone alleviates myocardial fibrosis via inhibition of Ets‑1 in mice with experimental autoimmune myocarditis. Exp Ther Med 23: 369, 2022.
APA
Wang, W., Wang, B., Cao, X., & Liu, Y. (2022). Spironolactone alleviates myocardial fibrosis via inhibition of Ets‑1 in mice with experimental autoimmune myocarditis. Experimental and Therapeutic Medicine, 23, 369. https://doi.org/10.3892/etm.2022.11296
MLA
Wang, W., Wang, B., Cao, X., Liu, Y."Spironolactone alleviates myocardial fibrosis via inhibition of Ets‑1 in mice with experimental autoimmune myocarditis". Experimental and Therapeutic Medicine 23.6 (2022): 369.
Chicago
Wang, W., Wang, B., Cao, X., Liu, Y."Spironolactone alleviates myocardial fibrosis via inhibition of Ets‑1 in mice with experimental autoimmune myocarditis". Experimental and Therapeutic Medicine 23, no. 6 (2022): 369. https://doi.org/10.3892/etm.2022.11296