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Inhibition of cardiac hypertrophy by aromadendrin through down-regulating NFAT and MAPKs pathways

Author:
Cui, Sumei, Cui, Yuqian, Li, Yuan, Zhang, Yongtao, Wang, Hao, Qin, Weidong, Chen, Xiaomei, Ding, Shifang, Wu, Dawei, Guo, Haipeng
Source:
Biochemical and biophysical research communications 2018 v.506 no.4 pp. 805-811
ISSN:
0006-291X
Subject:
body weight, cardiac output, cardiomyocytes, diabetes, drugs, fibrosis, genes, heart failure, hypertrophy, malondialdehyde, medicine, mice, mitogen-activated protein kinase, models, peroxidation, phenylephrine, protective effect, protein synthesis, risk factors, therapeutics
Abstract:
Cardiac hypertrophy is a maladaptive response to pressure overload and it's an important risk factor for heart failure and other adverse cardiovascular events. Aromadendrin (ARO) has remarkable anti-lipid peroxidation efficacy and is a potential therapeutic medicine for the management of diabetes and cardiovascular diseases. In this study, we established the cardiac hypertrophy cell model in rat neonatal ventricular cardiomyocytes (RNVMs) with phenylephrine. The cell model was characterized by the increased protein synthesis and cardiomyocyte size, which can be normalized by ARO treatment in both concentration- and time-dependent manner. In transverse aortic constriction (TAC) induced cardiac hypertrophy model, ARO administration improved the impairment of cardiac function and alleviated the cardiac hypertrophy indicators, like ventricular mass/body weight, myocyte cross-sectional area, and the expression of ANP, BNP and Myh7. ARO treatment also suppressed the cardiac fibrosis and the correlated fibrogenic genes. Our further investigation revealed ARO could down-regulate pressure overload-induced Malondialdehyde (MDA) and 4-HNE expression, restore the decrease of GSH/GSSG ratio, meanwhile prevent nuclear translocation of NFAT and the activation of MAPKs pathways. Collectively, ARO has a protective effect against experimental cardiac hypertrophy in mice, suggesting its potential as a novel therapeutic drug for pathological cardiac hypertrophy.
Agid:
6225396