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.
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Physical exercise can upregulate an important signalling pathway involved in cardiomyocyte proliferation/regeneration, such as the growth factor neuregulin-1 and its tyrosine kinase receptors ErbB2 and ErbB4.
“or of an important signalling pathway involved in cardiomyocyte proliferation/regeneration such as the growth factor neuregulin-1 and its tyrosine kinase receptors ErbB2 and ErbB4 168”
From Exercise benefits in cardiovascular diseases: From mechanisms to clinical implementation (2023) · cites this paper as [168]
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- Authors
- Cai, M.-X., Shi, X.-C., Chen, T., Tan, Z.-N., Lin, Q.-Q., Du, S.-J., & Tian, Z.-J.
- Affiliations
- Weinan Normal University (CN)
- Xizang Minzu University (CN)
- Shaanxi Normal University (CN)
- Yanshan University (CN)
- Venue
- Life Sciences
- Publisher
- Elsevier BV
- Published
- 2016-03
- Volume
- 149
- Pages
- 1-9
- ISSN
- 0024-3205 (ISSN-L)
- OpenAlex
- W2274037364
- Cited by
- 101
- References
- 51
- Citations by year
- 2026: 5 · 2025: 13 · 2024: 5 · 2023: 8 · 2022: 16 · 2021: 9 · 2020: 14 · 2019: 6 · 2018: 13 · 2017: 9 · 2016: 3
- FWCI
- 5.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Life Sciences (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (31040045, 31171141, 31371199)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Effects of Exercise
- Keywords
- exercise training, myocardial infarction, neuregulin-1, ErbB signaling, cardiac repair, cardiac regeneration, cardiomyocyte proliferation, cardiomyocyte apoptosis, PI3K/Akt signaling, ERBB2, ErbB4, AG1478, cardioprotection
- MeSH terms
- Animals, Disease Models, Animal, Male, Myocardial Infarction, Physical Conditioning, Animal, Quinazolines, Rats, Sprague-Dawley, Oncogene Proteins v-erbB, Tyrphostins, Neuregulin-1, Rats
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