title: Granulocyte colony stimulating factor/macrophage colony stimulating factor improves postinfarct ventricular function by suppression of border zone remodelling in rats.
abstract: 1. The aim of the present study was to examine the effects of mobilization of bone marrow cells by granulocyte colony stimulating factor (G-CSF) and macrophage colony stimulating factor (M-CSF) on ventricular function after myocardial infarction (MI). 2. After ligation of the left coronary artery, rats were divided into a vehicle control group (MI group) and a CSF-treated group (MI-CSF group). Rats in the MI-CSF group received a combination of G-CSF (50 microg/kg per day) and M-CSF (10(6) IU/kg per day) for 5 days after MI. Two weeks after MI, hearts were isolated and perfused with a Krebs' buffer and their functional responses to step-wise elevation of left ventricular end-diastolic pressure (LVEDP) were assessed. In histological analysis, proliferating cells and bone marrow-derived cells were identified by antibodies against Ki-67 and c-kit and organization of collagen was examined by picrosirius red staining. The mRNA levels of transforming growth factor (TGF)-beta(1), collagen type I and collagen type III were measured by quantitative reverse transcription-polymerase chain reaction. 3. Numbers of Ki-67- and c-kit-positive cells in the infarct border zone after MI were increased by CSF treatment, but few of those cells were stained by anti-alpha-sarcomeric actin. The levels in mRNA of TGF-beta1 and collagen type I in the infarct border zone were higher in the CSF-treated group compared with the MI group. Although CSF treatment did not reduce ventricular hypertrophy or infarct size at 2 weeks after MI, it did significantly improved the response of left ventricular developed pressure to step-wise elevation of LVEDP. This effect was mimicked by treatment with M-CSF alone. The functional improvement by CSF treatment was correlated with suppression of enlargement of the infarct-non-infarct border associated with infarct expansion. Collagen fibres in the border zone were thicker and orientated more orderly in the CSF-treated group than in the untreated group. 4. The results suggest that G-CSF/M-CSF treatment improves contractile function of the ventricle after infarction, presumably by acceleration of infarct repair and suppression of remodelling in the border zone.
authors.affiliation: Second Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan. tmiki@sapmed.ac.jp
authors.forename: Takayuki
authors.initials: T
authors.lastname: Miki
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Miura
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nishino
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Yano
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: Nobuyuki
authors.initials: N
authors.lastname: Ura
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Shimamoto
mesh_terms: D000818:Animals; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology / Q000627:therapeutic use*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology / Q000627:therapeutic use*; D066298:In Vitro Techniques; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016276:Ventricular Function / Q000187:drug effects / Q000502:physiology; D020257:Ventricular Remodeling / Q000187:drug effects* / Q000502:physiology
chemical_list: D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor