title: Effects of combination of proliferative agents and erythropoietin on left ventricular remodeling post-myocardial infarction.
abstract: Erythropoietin (EPO) has the potential to improve ischemic tissue by mobilizing endothelial progenitor cells and enhancing neovascularization. We hypothesized that combining EPO with human chorionic gonadotrophin (hCG) would improve post-myocardial infarction (MI) effects synergistically.
  
  
  METHODS
  After MI, five to seven animals were randomly assigned to each of the following treatments: control; hCG; EPO; hCG + EPO, and prolactin (PRL) + EPO. Follow-up echocardiograms were performed to assess cardiac structure and function. Apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay and western blot analysis for apoptosis-related proteins, and cell proliferation by immunostaining for Ki67 and c-kit cells.
  
  
  RESULTS
  The MI-mediated increased chamber systolic dimension (p < 0.05 in controls) was attenuated by hCG, EPO, and hCG + EPO (p < 0.05 vs. control) but not PRL + EPO. Similarly all treatment groups, except PRL + EPO, reduced MI-induced increases (p < 0.05 vs. control) in ejection fraction (EF). The functional improvement in the EPO-treated groups was accompanied by increased capillary density. Apoptosis was markedly reduced in all treated groups. Significantly more cardiac c-kit(+) cells were found in the hCG + EPO group.
  
  
  CONCLUSIONS
  Our findings revealed that EPO, hCG, or their combination ameliorate cardiac remodeling post-MI. Whereas EPO stimulates neovascularization only and hCG + EPO stimulates c-kit+ cell proliferation. These data suggest that combining mobilizing and proliferative agents adds to the durability and sustainability of cytokine-based therapies for remodeling post-MI.
authors.affiliation: Interdisciplinary Stem Cell Institute, Leonard M. Miller School of Medicine, University of Miami, Miami, Florida, USA.
authors.forename: Rosemeire M
authors.initials: RM
authors.lastname: Kanashiro-Takeuchi
authors.forename: Lauro M
authors.initials: LM
authors.lastname: Takeuchi
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Hatzistergos
authors.forename: Henry
authors.initials: H
authors.lastname: Quevedo
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Selem
authors.forename: Adriana V
authors.initials: AV
authors.lastname: Treuer
authors.forename: Courtney
authors.initials: C
authors.lastname: Premer
authors.forename: Wayne
authors.initials: W
authors.lastname: Balkan
authors.forename: Irene
authors.initials: I
authors.lastname: Margitich
authors.forename: Yun
authors.initials: Y
authors.lastname: Song
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Hu
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Hare
mesh_terms: D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D006063:Chorionic Gonadotropin / Q000378:metabolism; D004452:Echocardiography / Q000379:methods; D004921:Erythropoietin / Q000627:therapeutic use*; D006801:Humans; D020287:In Situ Nick-End Labeling; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D020257:Ventricular Remodeling
chemical_list: D006063:Chorionic Gonadotropin; D019394:Ki-67 Antigen; D004921:Erythropoietin; D019009:Proto-Oncogene Proteins c-kit