Exercise training activates neuregulin 1/ErbB signaling and promotes cardiac repair in a rat myocardial infarction model.
AIMS Exercise training (ET) has a cardioprotective effect and can alter the molecular response to myocardial infarction (MI) The Neuregulin 1 (NRG1)/ErbB signaling plays a critical role in cardiac repair and regeneration in the failing heart. We sought to investigate whether ET following MI could activate the NRG1/ErbB signaling and promote cardiac repair and regeneration. MAIN METHODS Male Sprague Dawley rats were used to establish the MI model. Exercise trained animals were subjected to four weeks of exercise (16m/min, 50min/d, 5d/wk) following the surgery. AG1478 was used as an inhibitor of ErbB (1mg/kg body weight, administered i.v. every other day during the process of training) NRG1/ErbB signaling activation, cardiomyocyte (CM) proliferation and apoptosis were evaluated. KEY FINDINGS In the exercise trained rats, NRG1 expression was up regulated and ErbB/PI3K/Akt signaling was activated compared with the MI group. In addition, ET preserved heart function accompanied with increased numbers of BrdU( CMs, PCNA( CMs and c kit( cells, and reduced apoptosis level in the MI rats. In contrast, blocking ErbB signaling by AG1478 attenuated the ET induced cardiac repair and regeneration. SIGNIFICANCE ET up regulates NRG1 expression and activates ErbB2, ErbB4 and PI3K/Akt signal transduction to promote cardiac repair through endogenous regeneration. Activation of ErbB may be an underlying mechanism for the ET induced cardiac repair and regeneration following MI.
Life sciences