title: Granulocyte colony-stimulating factor attenuates early ventricular expansion after experimental myocardial infarction.
abstract: OBJECTIVE
  In the early phase after transmural myocardial infarction (MI), the infarcted myocardium undergoes replacement by scar tissue, which is essential for preserving the structural integrity of the infarcted tissue. Transforming growth factor (TGF)-beta1, which is known as a fibrotic cytokine, plays a pivotal role in the reparative fibrosis after MI. It is reported that granulocyte colony-stimulating factor (G-CSF) can accelerate wound healing. The aim of our study was to investigate the effect of G-CSF on early ventricular expansion after MI.
  
  
  METHODS
  MI was induced by ligation of the left coronary artery in male Wistar rats. G-CSF (20 microg/kg/day, MI-GCSF) or saline (MI-saline) was injected subcutaneously 3 h after MI and every 24 h thereafter for 7 days. Hemodynamic and echocardiographic studies were performed at 14 days. Expression of TGF-beta1 and procollagen type I and type III mRNA in both the infarcted and noninfarcted areas was studied by quantitative RT-PCR at 1, 3, 7, and 14 days after MI. Histological studies were performed at 7 days.
  
  
  RESULTS
  MI-GCSF had higher LV max dP/dt, lower LV end-diastolic pressure, and smaller LV end-diastolic and end-systolic dimensions compared to MI-saline. Infarct size was not different between MI-GCSF and MI-saline. Expression of TGF-beta1 mRNA in the infarcted area at 3 days was significantly higher in MI-GCSF than in MI-saline. Expression of procollagen type I and type III mRNA in the infarcted area at 3 days was higher in MI-GCSF compared to MI-saline, and the peak mRNA levels were earlier in MI-GCSF. In the noninfarcted area, there was no difference in TGF-beta1 mRNA expression between MI-GCSF and MI-saline. Histologically, collagen accumulation in the infarcted area at 7 days was more prominent in MI-GCSF than in MI-saline.
  
  
  CONCLUSIONS
  G-CSF treatment improves early post-infarct ventricular expansion through promotion of reparative collagen synthesis in the infarcted area, suggesting some beneficial effect of G-CSF on the infarct healing process.
authors.affiliation: Division of Cardiology, Department of Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Sugano
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Anzai
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Maekawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Kohno
authors.forename: Keitaro
authors.initials: K
authors.lastname: Mahara
authors.forename: Kotaro
authors.initials: K
authors.lastname: Naito
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ogawa
mesh_terms: D000818:Animals; D015153:Blotting, Western / Q000379:methods; D003094:Collagen / Q000096:biosynthesis / Q000235:genetics; D005355:Fibrosis; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D007150:Immunohistochemistry / Q000379:methods; D007958:Leukocyte Count; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology*; D009206:Myocardium / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D009504:Neutrophils / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D012333:RNA, Messenger; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D016179:Granulocyte Colony-Stimulating Factor; D003094:Collagen