title: Macrophage colony-stimulating factor treatment after myocardial infarction attenuates left ventricular dysfunction by accelerating infarct repair.
abstract: OBJECTIVE
  We aimed to determine the effects of macrophage colony-stimulating factor (M-CSF) and granulocyte colony-stimulating factor (G-CSF) treatment on both the repair process and ventricular function after myocardial infarction (MI).
  
  
  BACKGROUND
  The M-CSF and G-CSF have multiple potential effects on cells involved in wound repair.
  
  
  METHODS
  Myocardial infarction was induced by 45- or 90-min coronary occlusion and reperfusion in rats with or without subsequent injection of M-CSF (10(6) IU/kg/day) or G-CSF (50 microg/kg/day) for five days. We examined histology and messenger ribonucleic acid (mRNA), and assessed left ventricular function in situ using a conductance catheter.
  
  
  RESULTS
  Five days after MI, M-CSF increased the number of ED-1-positive cells, mRNA levels of transforming growth factor-beta-1, collagen I and III, and collagen fibers within the infarct. Fourteen days after MI, induced by 45-min ischemia, left ventricular end-systolic elastance (Ees) was reduced (1,191 +/- 87 mm Hg/ml vs. 1,812 +/- 150 mm Hg/ml) and both isovolumic relaxation time constant (tau) (11.9 +/- 0.9 ms vs. 8.5 +/- 0.4 ms) and left ventricular end-diastolic volume (LVEDV) (0.225 +/- 0.014 ml vs. 0.172 +/- 0.011 ml) increased versus sham-operated rats. These alterations after MI were attenuated by M-CSF (Ees = 1,650 +/- 146, tau = 9.7 +/- 0.7, LVEDV = 0.199 +/- 0.012) but not by G-CSF. This beneficial effect of M-CSF on Ees was also detected in hearts with MI induced by 90-min ischemia. Furthermore, M-CSF increased collagen content within infarcts and reduced the proportion of thin collagen fibers 14 days after MI. The Ees significantly correlated with infarct collagen content. Nevertheless, neither M-CSF nor G-CSF modified infarct size.
  
  
  CONCLUSIONS
  The M-CSF treatment attenuates deterioration of left ventricular function after MI by accelerating infarct repair.
authors.affiliation: Second Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Yano
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Miura
authors.forename: Peter
authors.initials: P
authors.lastname: Whittaker
authors.forename: Takayuki
authors.initials: T
authors.lastname: Miki
authors.forename: Jun
authors.initials: J
authors.lastname: Sakamoto
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Ichikawa
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Hironori
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Ohori
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Shimamoto
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D019394:Ki-67 Antigen / Q000032:analysis; D016173:Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D008297:Male; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000627:therapeutic use; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000235:genetics; D053773:Transforming Growth Factor beta1; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy* / Q000209:etiology; D016277:Ventricular Function, Left
chemical_list: D019394:Ki-67 Antigen; D012333:RNA, Messenger; D011994:Recombinant Proteins; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D016179:Granulocyte Colony-Stimulating Factor; D016173:Macrophage Colony-Stimulating Factor; D003094:Collagen