Eplerenone regulates hypertrophy in heart failure by microRNA-208a inhibiting on THRAP1

The influence of eplerenone on HF and some mechanism have been reported. However, research on the effect of eplerenone on the expression of miR-208a and THRAP1 in the treatment of HF is limited. Thus, in this study, we aimed to study the relationship between miR-208a and eplerenone treatment in heart failure (HF). SD rats (N = 40) were randomly divided into 4 groups after modeling the transverse aortic constriction (TAC) at 12 weeks (n = 10 in each group): control group (0.9% normal saline of 2 ml/day), eplerenone group (eplerenone of 5.1 mg/ kg/day), angiotensin converting enzyme inhibitor (ACEI) group (captopril of 3.86 mg/kg/day + metoprolol of 5.1 mg/kg/day) and combined group (eplerenone of 5.1 mg/kg/day + captopril of 3.86 mg/kg/day + metoprolol of 5.1 mg/kg/day). The levels of brain natriuretic peptide (BNP), left ventricular ejection fraction (LVEF), left ventricular end-systolic dimension (LVDs) and left ventricular end-diastolic dimension (LVDd) were measured. The expression of miR-208a and THRAP1 were also evaluated. In the eplerenone group, LVEF was significantly higher and BNP was significantly lower when compared to the control. After treatment with eplerenone at the beginning of HF following TAC, the level of LVEF increased and BNP decreased compared to the control group at 8 weeks. The level of serum potassium in eplerenone group was much higher than the control (P<0.05). The expression of miR-208a was significantly decreased in eplerenone group compared with the control (P<0.05), while the value of THRAP1 increased. The expression of THRAP1 in the group treated with anti-miR-208a increased significantly compared to controls (P<0.001). In conclusion, eplerenone not only improves HF but also reverses cardiac hypertrophy. As an effective medicine, eplerenone can treat heart failure via the miR-208a/THRAP1 pathway.