Downregulation of amphiregulin improves cardiac hypertrophy via attenuating oxidative stress and apoptosis

Abstract

Abstract Amphiregulin (AREG) is a ligand of epidermal growth factor receptor and participates in the fibrosis of multiple organs. However, whether AREG can regulate hypertrophic cardiomyopathy is not well known. This research aims to explore the effect of AREG on cardiac hypertrophy, and whether the oxidative stress and apoptosis was involved in the influence of AREG on cardiac hypertrophy. Angiotensin (Ang) II induced cardiac hypertrophy in mice and neonatal rat cardiomyocytes (NRCMs) or HL-1 cells in vitro. AREG expressions raised in the heart of mice. After AREG downregulation, the increases of Ang II induced cardiac weight and cardiomyocytes area were inhibited. Down-regulation of AREG could inhibit Ang II induced the increases of atrial natriuretic peptide, brain natriuretic peptide, beta-myosin heavy chain in the heart of mice, and NRCMs and HL-1 cells. The enhancement of oxidative stress in mice heart with Ang II treatment was alleviated by AREG knockdown. The raises of Ang II induced Bax and cleaved caspase3 in mice heart were inhibited by AREG downregulation. AREG downregulation reduced myocardial hypertrophy via inhibition of oxidative and apoptosis. AREG may be a target for future cardiac hypertrophy treatment.

Keywords

• Amphiregulin
• Cardiac hypertrophy
• Oxidative stress
• Apoptosis