TY - JOUR AB - 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. AD - Department of Cardiology, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250033, P.R. China Department of General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China AU - Wang,Wen-Ke AU - Wang,Ben AU - Cao,Xue-Hu AU - Liu,Yu-Sheng DA - 2022/06/01 DO - 10.3892/etm.2022.11296 IS - 6 JO - Exp Ther Med KW - spironolactone myocardial fibrosis experimental autoimmune myocarditis E26 transformation‑specific sequence‑1 PY - 2022 SN - 1792-0981 1792-1015 SP - 369 ST - Spironolactone alleviates myocardial fibrosis via inhibition of Ets‑1 in mice with experimental autoimmune myocarditis T2 - Experimental and Therapeutic Medicine TI - Spironolactone alleviates myocardial fibrosis via inhibition of Ets‑1 in mice with experimental autoimmune myocarditis UR - https://doi.org/10.3892/etm.2022.11296 VL - 23 ER -