Valsartan inhibits RhoA‑ROCK2‑MYL pathway in rat model of alcoholic cardiomyopathy

Li,Luyifei; Jing,Ling; Zhao,Jiyi; Lv,Jiachen; Yang,Wen; Li,Weimin; Zhou,Lijun

doi:10.3892/etm.2019.8079

Valsartan inhibits RhoA‑ROCK2‑MYL pathway in rat model of alcoholic cardiomyopathy

Authors:
- Luyifei Li
- Ling Jing
- Jiyi Zhao
- Jiachen Lv
- Wen Yang
- Weimin Li
- Lijun Zhou
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Affiliations: Department of Internal Critical Illness, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150000, P.R. China, Department of The Fourth Cardiovascular, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150000, P.R. China, Department of Colorectal Surgery, The Tumor Hospital of Harbin Medical University, Harbin, Heilongjiang 150000, P.R. China, Department of The First Nephrology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150000, P.R. China, Department of The Fifth Cardiovascular, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150000, P.R. China
Published online on: October 7, 2019 https://doi.org/10.3892/etm.2019.8079
Pages: 4313-4321
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study aimed to investigate variations in the Ras homolog gene family, member A (RhoA)‑Rho‑associated protein kinase 2 (ROCK2)‑myosin light chain (MYL) pathway in a rat model of alcoholic cardiomyopathy (ACM) and the role of angiotensin‑converting enzyme inhibitor drugs. Rat models of ACM were established via alcoholic gavage + free access to alcohol. The structural and functional changes of the heart were analyzed by hematoxylin‑eosin staining, Masson's trichrome staining, immunohistochemistry staining, western blotting and fluorescence quantitative polymerase chain reaction. A total of 16 weeks later, a decreased ejection fraction and left ventricular fractional shortening in the alcohol group compared with the control group were demonstrated resulting in an increased left ventricular end diastolic diameter. These adverse effects were ameliorated following treatment with valsartan. In addition, the alcohol group revealed a disorganized arrangement of myocardial filaments, which was improved upon treatment with valsartan. RhoA and ROCK2 protein expression significantly increased in myocardial cells in the alcohol compared with the control group. Following drug intervention with valsartan, expression of RhoA and ROCK2 proteins were inhibited in the alcohol group. Furthermore, significantly elevated RhoA and ROCK2 and decreased MYL protein and mRNA expression in the alcohol group was demonstrated compared with the control group. Administration of valsartan reversed the expression profile of RhoA, ROCK and MYL in ACM. Expression of RhoA and ROCK were elevated with downregulation of MYL resulting in heart failure. However, the angiotensin receptor antagonist diminished the expression of RhoA and ROCK and enhanced the expression of MYL. The results of the present study suggest a curative effect of valsartan in ACM.

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