Cardiac contractility modulation improves left ventricular systolic function partially via miR-25 mediated SERCA2A...

The purpose of this study was to investigate the underlying mechanism of cardiac contractility modulation (CCM) in improving trans aortic constriction (TAC)-induced heart failure (HF) left ventricular (LV) systolic function. A total of 25 New Zealand white rabbits were randomly divided into 5 groups: sham operation group (SHM), TAC-induced HF group (HF), TAC-induced HF followed by CCM stimulation group (HF + CCM), TAC-induced HF followed by injection of anti-miR-25 group (HF + anti-miR-25), TAC-induced HF followed by CCM stimulation and AAV9-miR-25 injection group (HF + CCM + miR-25). CCM current was performed 6 hours a day for 4 weeks. The left ventricle ejection fraction (LVEF) was measured by ultrasound. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were used for measuring RNA and protein levels. The sarcoplasmic reticulum calcium ATPase (SERCA2A) and LVEF were reduced, while the miR-25 expression was improved in HF group compared to SHM group. Conversely, the SERCA2A and LVEF were improved, and the miR-25 reduced in the HF + CCM and the HF + anti-miR-25 groups compared to the HF group. Moreover, the SERCA2A and LVEF were reduced, while the miR-25 was improved in the HF + CCM + miR-25 group compared to the HF + CCM group. CCM is a potentially effective procedure for improving LV systolic function, which might partially by inhibiting miR-25 expression, further improved SERCA2A expression in TAC HF models.