title: Postinfarction Cardiac Remodeling Proceeds Normally in Granulocyte Colony-Stimulating Factor Knockout Mice.
abstract: Treatment with granulocyte colony-stimulating factor (G-CSF) reportedly mitigates postinfarction cardiac remodeling and dysfunction. We herein examined the effects of G-CSF knockout (G-CSF-KO) on the postinfarction remodeling process in the hearts of mice. Unexpectedly, the acute infarct size 24 hours after ligation was similar in the two groups. At the chronic stage (4 weeks later), there was no difference in the left ventricular dimension, left ventricular function, or histological findings, including vascular density, between the two groups. In addition, expression of vascular endothelial growth factor (VEGF) was markedly up-regulated in hearts from G-CSF-KO mice, compared with wild-type mice. Microarray failed in detecting up-regulation of VEGF mRNA, whereas G-CSF administration significantly decreased myocardial VEGF expression in mice, indicating that G-CSF post-transcriptionally down-regulates VEGF expression. When G-CSF-KO mice were treated with an anti-VEGF antibody (bevacizumab), cardiac remodeling was significantly aggravated, with thinning of the infarct wall and reduction of the cellular component, including blood vessels. In the granulation tissue of bevacizumab-treated hearts 4 days after infarction, vascular development was scarce, with reduced cell proliferation and increased apoptosis, which likely contributed to the infarct wall thinning and the resultant increase in wall stress and cardiac remodeling at the chronic stage. In conclusion, overexpression of VEGF may compensate for the G-CSF deficit through preservation of cellular components, including blood vessels, in the postinfarction heart.
authors.affiliation: Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu, Japan; Department of Cardiology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Morishita
authors.affiliation: Department of Cardiology, Gifu University Graduate School of Medicine, Gifu, Japan; Department of Internal Medicine, Asahi University School of Dentistry, Mizuho, Japan. Electronic address: gt@dent.asahi-u.ac.jp.
authors.forename: Genzou
authors.initials: G
authors.lastname: Takemura
authors.affiliation: Department of Cardiology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Tsujimoto
authors.affiliation: Department of Cardiology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Kanamori
authors.affiliation: Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu, Japan; Department of Cardiology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Hideshi
authors.initials: H
authors.lastname: Okada
authors.affiliation: Department of Informative Clinical Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Chousa
authors.affiliation: Department of Informative Clinical Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Seiko
authors.initials: S
authors.lastname: Ushimaru
authors.affiliation: Department of Cardiology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Mikami
authors.affiliation: Department of Cardiology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Itta
authors.initials: I
authors.lastname: Kawamura
authors.affiliation: Department of Cardiology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Takeyama
authors.affiliation: Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu, Japan; Department of Cardiology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Kawaguchi
authors.affiliation: Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu, Japan; Department of Cardiology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Takatomo
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Department of Cardiology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Goto
authors.affiliation: Department of Cardiology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Morishita
authors.affiliation: Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu, Japan; Department of Cardiology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ushikoshi
authors.affiliation: Department of Cardiology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Kawasaki
authors.affiliation: Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Ogura
authors.affiliation: Department of Cardiology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Minatoguchi
mesh_terms: D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D006097:Granulation Tissue / Q000378:metabolism / Q000473:pathology; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood / Q000172:deficiency / Q000235:genetics*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000139:chemically induced / Q000473:pathology*; D009206:Myocardium / Q000473:pathology; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling / Q000235:genetics*
chemical_list: D042461:Vascular Endothelial Growth Factor A; D016179:Granulocyte Colony-Stimulating Factor