title: Effects of G-CSF on cardiac remodeling and arterial hyperplasia in rats.
abstract: Although granulocyte colony-stimulating factor (G-CSF) has been shown to prevent cardiac remodeling after acute myocardial infarction, the mechanism and safety of G-CSF treatment acute myocardial infarction remain controversial. The purpose of the present study was to investigate in a rat model the mechanisms underlying the beneficial effect of G-CSF in acute myocardial infarction and to determine whether G-CSF treatment aggravates vascular remodeling of injured artery after acute myocardial infarction. Sprague-Dawley rats received transplanted bone marrow cells from green fluorescent protein (GFP) transgenic rats. Acute myocardial infarction was induced by ligation of the left coronary artery. After 24 h, the right carotid artery was injured with a balloon catheter. G-CSF (100 microg/kg/day) or saline was injected subcutaneously for 5 consecutive days after induction of acute myocardial infarction. G-CSF treatment significantly improved left ventricle function and reduced infarct size in rats with acute myocardial infarction. Expression of mRNA for the angiogenic cytokines was significantly higher in the infarction border area in the G-CSF group than in the control group. The surviving cardiomyocytes in infarction area were more in the G-CSF group. GFP-positive cells were gathered in the infarction border area in both groups; G-CSF did not increase cardiac homing of GFP-positive bone marrow cells in contrast to control group. Most GFP-positive cells were CD68-positive (macrophages). It was difficult to find bone marrow-derived cardiomyocytes in the infarcted area. G-CSF treatment inhibited neointima formation and increased reendothelialization of the injured artery. GFP-positive cells were identified most in the adventitia of the injured artery. A few cells in the neointima and reendothelialization were GFP positive. In conclusion, administration of G-CSF appears to be effective for treatment of left ventricular remodeling after acute myocardial infarction and does not aggravate vascular remodeling. The effect of G-CSF on cardiac and vascular remodeling may occur mainly through a direct action on the heart and arteries.
authors.affiliation: Department of Internal Medicine, Nihon University School of Medicine, Tokyo 173-8610, Japan.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Li
authors.forename: Noboru
authors.initials: N
authors.lastname: Fukuda
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Yokoyama
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kusumi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Hagikura
authors.forename: Taro
authors.initials: T
authors.lastname: Kawano
authors.forename: Tadateru
authors.initials: T
authors.lastname: Takayama
authors.forename: Taro
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Aya
authors.initials: A
authors.lastname: Satomi
authors.forename: Junko
authors.initials: J
authors.lastname: Honye
authors.forename: Hideo
authors.initials: H
authors.lastname: Mugishima
authors.forename: Masako
authors.initials: M
authors.lastname: Mitsumata
authors.forename: Satoshi
authors.initials: S
authors.lastname: Saito
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D016026:Bone Marrow Transplantation / Q000379:methods; D002339:Carotid Arteries / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020212:Carotid Artery Injuries / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control; D016207:Cytokines / Q000235:genetics; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D015870:Gene Expression / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006965:Hyperplasia; D007150:Immunohistochemistry; D007279:Injections, Subcutaneous; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D020257:Ventricular Remodeling / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D014841:von Willebrand Factor / Q000378:metabolism; D000097382:CD68 Molecule
chemical_list: D000199:Actins; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D016207:Cytokines; D016179:Granulocyte Colony-Stimulating Factor; D049452:Green Fluorescent Proteins; D014841:von Willebrand Factor; C067980:CD68 antigen, human; D000097382:CD68 Molecule