Inhibition of cardiac hypertrophy by aromadendrin through down-regulating NFAT and MAPKs pathways
- Department of Emergency, Qilu Hospital of Shandong University, Jinan (China)
- Center for Reproductive Medicine, Qilu Hospital of Shandong University, Jinan (China)
- Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China)
- Department of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao (China)
Highlights: • Aromadendrin prevented cardiac hypertrophy and dysfunction after pressure-overload. • ARO suppressed protein synthesis and fetal gene reactivation in vitro. • ARO attenuated cardiac fibrosis and oxidative stress in cardiac hypertrophy. • ARO suppressed NFAT nuclear translocation and inhibited MAPKs pathway activations. • ARO has the potential application prospects for cardiac hypertrophy treatment. 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.
- OSTI ID:
- 23105666
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 506, Issue 4; Other Information: Copyright (c) 2018 Elsevier Inc. All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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