title: Erythropoietin Decreases the Occurrence of Myocardial Fibrosis by Inhibiting the NADPH-ERK-NF-x03BA;B Pathway.
abstract: OBJECTIVE
  The aim of this study was to investigate the protective role of erythropoietin (EPO) against myocardial fibrosis (MF).
  
  
  METHODS
  Pressure-overloaded rats were established by abdominal aortic constriction, the rats were randomly divided in a double-blind manner into 3 groups (n = 12 for each group): sham-operated rats (sham), operated rats receiving physiological saline (vehicle) and operated rats receiving 4,000 U/kg rhEPO (EPO group). The vehicle and drugs were administered to rats by intraperitoneal injection. In addition, cultured adult rat cardiac fibroblasts (CFs) were utilized to investigate the role of EPO in CF proliferation and collagen secretion.
  
  
  RESULTS
  After 4 weeks, besides an increase in blood pressure, myocardial hypertrophy, collagen deposition in the myocardium and decreased cardiac function were observed in the pressure-overloaded rats. The expression of NADPH oxidase (Nox2 and Nox4) and inflammatory cytokines (CD45, F4/80 and MCP-1) was also significantly increased. All these alterations were prevented by EPO. TGF-β promoted CF proliferation, collagen secretion, ROS production and Nox2/Nox4 expression, which was inhibited by EPO. In addition, the TGF-β-induced increase of ERK1/2 phosphorylation and NF-x03BA;B expression were attenuated by EPO.
  
  
  CONCLUSIONS
  EPO inhibited rat MF induced by pressure overload and improved myocardial function by decreasing CF proliferation and differentiation via inhibition of the NADPH-ERK-NF-x03BA;B pathway.
authors.affiliation: Department of Physiology and Tangshan Key Laboratory for Preclinical and Basic Research on Chronic Diseases, School of Basic Medical Science, North China University of Science and Technology, Tangshan, China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Wang
authors.forename: Xiu-Hong
authors.initials: XH
authors.lastname: Yang
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Wang
authors.forename: Shu-Min
authors.initials: SM
authors.lastname: Li
authors.forename: Na
authors.initials: N
authors.lastname: Sun
authors.forename: Tian
authors.initials: T
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D002478:Cells, Cultured; D004311:Double-Blind Method; D004719:Endomyocardial Fibrosis / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control*; D004921:Erythropoietin / Q000494:pharmacology / Q000627:therapeutic use*; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology; D007150:Immunohistochemistry; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D009206:Myocardium / Q000473:pathology; D009249:NADP / Q000187:drug effects / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D016212:Transforming Growth Factor beta; D004921:Erythropoietin; D009249:NADP