Metformin ameliorates cardiac conduction delay by regulating microRNA-1 in mice.

Cardiac conduction delay may occur as a common complication of several cardiac diseases. A few therapies and drugs have a good effect on cardiac conduction delay. Metformin (Met) has a protective effect on the heart. This study's aim was to investigate whether Met could ameliorate cardiac conduction delay and its potential mechanism. Cardiac-specific microRNA-1 (miR-1) transgenic (TG) and myocardial infarction (MI) mouse models were used. Mice were administered with Met in an intragastric manner. We found that the expression of miR-1 was significantly up-regulated in H2O2 treated cardiomyocytes as well as in TG and MI mice. The protein levels of inwardly rectifying potassium channel 2.1 (Kir2.1) and Connexin43 (CX43) were down-regulated both in cardiomyocytes treated with H2O2 as well as cardiac tissues of TG and MI mice, as compared to their controls. Furthermore, the PR and QT intervals were prolonged, action potential duration (APD) was delayed, and conduction velocity (CV) was reduced, with upregulation of miR-1 in the hearts. In the meanwhile, intercalated disc injuries were found in the hearts of MI mice. Interestingly, Met can noticeably inhibit miR-1 upregulation and attenuate the changes mentioned above. Taken together, this suggested that Met could play an important role in improving cardiac conduction delay through inhibition of miR-1 expression. Our study proposes that Met is a potential candidate for the treatment of cardiac conduction delay and provides a new idea of treating arrhythmia with a drug.