Schisandrin A protects against isoproterenol-induced chronic heart failure via miR-155

Schisandrin A (Sch A) has a protective effect on cardiomyocytes. Circulating miR-155 levels are related to chronic heart failure (CHF). The present study aimed to clarify the role and the molecular mechanism of Sch A in CHF. C57BL/6JGpt mice were used for an isoproter- enol (ISO)-induced CHF model to collect heart samples. Echocardiography was employed to detect heartbeat indica- tors. The degree of myocardial hypertrophy was evaluated based on the measurement of heart weight (HW), body weight (BW) and tibia length (TL) and the observation using hematox- ylin-eosin staining. Sprague-Dawley rats were purchased for the separation of neonatal rat ventricular myocytes (NRVMs), which were treated with ISO for 24 h. Transfection regulated the level of miR-155. The viability of NRVMs was detected via MTT assay. The mRNA and protein levels were measured via reverse transcription-quantitative PCR and western blot- ting and immunofluorescence was used to detect the content of α-smooth muscle actin (α-SMA). Treatment with ISO resulted in rising left ventricular posterior wall thickness, intra-ventricular septum diastole, left ventricular end diastolic diameter, left ventricular end systolic diameter, HW/BW, HW/TL and falling ejection fraction and fractional short- ening, the trend of which could be reversed by Sch A. Sch A ameliorated myocardial hypertrophy in CHF mice. In addi- tion, Sch A inhibited ISO-induced upregulated expressions of atrial natriuretic peptide, B-type natriuretic peptide, B-myosin heavy chain and miR-155 in myocardial tissue. Based on the results in vitro, Sch A had no significant effect on the viability of NRVMs when its concentration was <24 µmol/l. Sch A inhibited the levels of miR-155, α-SMA and the phosphoryla- tion levels of AKT and cyclic AMP response-element binding protein (CREB) in ISO-induced NRVMs, which was reversed by the upregulation of miR-155. Schisandrin A mediated the AKT/CREB signaling pathway to prevent CHF by regulating the expression of miR-155, which may shed light on a possible therapeutic target for CHF.