Cytokine therapy prevents left ventricular remodeling and dysfunction after myocardial infarction through neovascularization.
Pretreatment with a combination of granulocyte colony-stimulating factor (G-CSF) and stem cell factor (SCF) has been reported to attenuate left ventricular (LV) remodeling after acute myocardial infarction (MI). We here examined whether the cytokine treatment started after MI has also beneficial effects. Anterior MI was created in the recipient mice whose bone marrow had been replaced with that of transgenic mice expressing enhanced green fluorescent protein (GFP). We categorized mice into five groups according to the following treatment: 1) saline; 2) administration of G-CSF and SCF from 5 days before MI through 3 days after; 3) administration of G-CSF and SCF for 5 days after MI; 4) administration of G-CSF alone for 5 days after MI; 5) administration of SCF alone for 5 days after MI. All the three treatment groups with G-CSF showed less LV remodeling and improved cardiac function and survival rate after MI. The number of capillaries, which express GFP, was increased and the number of apoptotic cells was decreased in the border area of all the treatment groups with G-CSF. Even if the cytokine treatment is started after MI, it could prevent LV remodeling and dysfunction after MI--at least in part--through an increase in neovascularization and a decrease in apoptosis in the border area.
Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, Chiba, Japan.
Masashi
M
Ohtsuka
Hiroyuki
H
Takano
Yunzeng
Y
Zou
Haruhiro
H
Toko
Hiroshi
H
Akazawa
Yingjie
Y
Qin
Masashi
M
Suzuki
Hiroshi
H
Hasegawa
Haruaki
H
Nakaya
Issei
I
Komuro
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001854:Bone Marrow Cells / Q000187:drug effects / Q000502:physiology; D016026:Bone Marrow Transplantation; D019070:Cell Lineage; D002465:Cell Movement / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D049452:Green Fluorescent Proteins; D006439:Hemodynamics / Q000187:drug effects; D008164:Luminescent Proteins / Q000032:analysis / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008833:Microcirculation; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D019089:Stem Cell Factor / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D020257:Ventricular Remodeling / Q000187:drug effects*
D008164:Luminescent Proteins; D019089:Stem Cell Factor; D016179:Granulocyte Colony-Stimulating Factor; D049452:Green Fluorescent Proteins