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.

The aim of the study was to determine the roles of microRNA (miR)-146a on myocardial infarction (MI)-induced heart failure and cardiac remodeling. Experiments were carried out in Sprague-Dawley rats treated with ligation of left coronary artery to induce heart failure, and in primary neonatal rat cardiac fibroblasts (CFs) and cardiomyocytes treated with angiotensin (Ang) II. Four weeks after MI, rats were injected with miR-146a antagomiR or agomiR via tail vein. After 2 weeks of injection, the rats were sacrificed. In MI rats, left ventricle (LV) ejection fraction and fractional shortening were reduced, and LV volumes in diastole and systole were increased, which were reversed by miR-146a antagomiR, and further exacerbated after miR-146a agomiR treatment. Administration of miR-146a antagomiR improved the decreases of LV {plus minus}dp/dt_max and LV systolic pressure (LVSP), and the increase in LV end-diastolic pressure (LVEDP) of MI rats, but miR-146a agomiR deteriorated the LV {plus minus}dp/dt _max, LVSP and LVEDP. The increases in the levels of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), collagen I and collagen III in the heart, and ST2 and norepinephrine in the serum of MI rats were inhibited by miR-146a antagomiR, but aggravated after miR-146a agomiR treatment. The increases of collagen I and collagen III levels induced by Ang II in CFs, and the increases of ANP and BNP levels induced by Ang II in cardiomyocytes were inhibited by miR-146a antagomiR, but aggravated by miR-146a agomiR. These results demonstrated that inhibition miR-146a improved cardiac dysfunction and cardiac remodeling in heart failure rats.

In this study, we investigated whether CD47 deficiency attenuates isoproterenol- (ISO-) induced cardiac remodeling in mice. Cardiac remodeling was induced by intraperitoneal (i.p.) injection of ISO (60 mg·kg^-1·d^-1 in 100 μl of sterile normal saline) daily for 14 days and was confirmed by increased levels of lactate dehydrogenase (LDH) and creatine kinase MB (CK-MB), increased heart weight to body weight (HW/BW) ratios, and visible cardiac fibrosis. Apoptosis was evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. Levels of malondialdehyde (MDA) and reactive oxygen species (ROS) were found to be significantly higher in the ISO group than in the control group, while superoxide dismutase (SOD) levels were suppressed in the ISO group. However, CD47 knockout significantly limited ISO-induced increases in LDH, CK-MB, and HW/BW ratios, cardiac fibrosis, oxidative stress, and apoptosis in the heart. In addition, CD47 deficiency also increased p-AMPK and LAMP2 expression and decreased HDAC3, cleaved Caspase-3, cleaved Caspase-9, LC3II, and p62 expression in cardiac tissues. In conclusion, CD47 deficiency reduced i.p. ISO-induced cardiac remodeling probably by inhibiting the HDAC3 pathway, improving AMPK signaling and autophagy flux, and rescuing autophagic clearance.

High salt can induce cardiac damage. The aim of this present study was to explore the effect and the mechanism of microRNA (miR)-142-3p on the cardiac fibrosis induced by high salt. Rats received high salt diet to induce cardiac fibrosis in vivo, and neonatal rat cardiac fibroblasts (NRCF) treated with sodium chloride (NaCl) to induce fibrosis in vitro. The fibrosis and mitochondrial autophagy levels were increased the heart and NRCF treated with NaCl, which were alleviated by miR-142-3p upregulation. The fibrosis and mitochondrial autophagy levels were elevated in NRCF after treating with miR-142-3p antagomiR. Optineurin (OPTN) expression was increased in the mitochondria of NRCF induced by NaCl, which was attenuated by miR-142-3p agomiR. OPTN downregulation inhibited the increases of fibrosis and mitochondrial autophagy levels induced by NaCl in NRCF. These results miR-142-3p could alleviate high salt-induced cardiac fibrosis via downregulation of OPTN to reduce mitophagy.