title: Exercise training activates neuregulin 1/ErbB signaling and promotes cardiac repair in a rat myocardial infarction model.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.affiliation: Institute of Sports and Exercise Biology, Shaanxi Normal University, Xi'an, Shaanxi, PR China.
authors.forename: Meng-Xin
authors.initials: MX
authors.lastname: Cai
authors.affiliation: Institute of Sports and Exercise Biology, Shaanxi Normal University, Xi'an, Shaanxi, PR China; College of Chemistry and Life Science, Weinan Normal University, Weinan, Shaanxi, PR China.
authors.forename: Xiu-Chao
authors.initials: XC
authors.lastname: Shi
authors.affiliation: Institute of Sports and Exercise Biology, Shaanxi Normal University, Xi'an, Shaanxi, PR China; Department of Sports and Exercise, Tibet University for Nationalities, Xianyang, Shaanxi, PR China.
authors.forename: Ting
authors.initials: T
authors.lastname: Chen
authors.affiliation: Institute of Sports and Exercise Biology, Shaanxi Normal University, Xi'an, Shaanxi, PR China.
authors.forename: Zhi-Nei
authors.initials: ZN
authors.lastname: Tan
authors.affiliation: College of Physical Education, Yanshan University, Qinhuangdao, PR China.
authors.forename: Qin-Qin
authors.initials: QQ
authors.lastname: Lin
authors.affiliation: Institute of Marine and Environmental Technology, Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD, United States.
authors.forename: Shao-Jun
authors.initials: SJ
authors.lastname: Du
authors.affiliation: Institute of Sports and Exercise Biology, Shaanxi Normal University, Xi'an, Shaanxi, PR China. Electronic address: tianzj2011@126.com.
authors.forename: Zhen-Jun
authors.initials: ZJ
authors.lastname: Tian
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism* / Q000628:therapy*; D020890:Neuregulin-1 / Q000096:biosynthesis*; D018739:Oncogene Proteins v-erbB / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D010805:Physical Conditioning, Animal / Q000379:methods*; D011799:Quinazolines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020032:Tyrphostins / Q000494:pharmacology
chemical_list: D020890:Neuregulin-1; C490580:Nrg1 protein, rat; D018739:Oncogene Proteins v-erbB; D011799:Quinazolines; D020032:Tyrphostins; C101044:RTKI cpd
keywords: Cardiac repair; Cardiomyocyte proliferation; Exercise training; Myocardial infarction; Neuregulin 1