Exercise training activates neuregulin 1/ErbB signaling and promotes cardiac repair in a rat myocardial infarction model.

Abstract

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.

• Authors: Meng-Xin Cai, Xiu-Chao Shi, Ting Chen, Zhi-Nei Tan, Qin-Qin Lin, Shao-Jun Du, Zhen-Jun Tian
• Journal: Life sciences (Life Sci) Vol. 149 Pg. 1-9 (Mar 15 2016) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 26892146 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 Elsevier Inc. All rights reserved.

Chemical References

• Neuregulin-1
• Nrg1 protein, rat
• Oncogene Proteins v-erbB
• Quinazolines
• Tyrphostins
• RTKI cpd

Topics

• Animals
• Disease Models, Animal
• Male
• Myocardial Infarction (metabolism, therapy)
• Neuregulin-1 (biosynthesis)
• Oncogene Proteins v-erbB (antagonists & inhibitors, biosynthesis)
• Physical Conditioning, Animal (methods)
• Quinazolines (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Tyrphostins (pharmacology)