title: G-CSF/SCF reduces inducible arrhythmias in the infarcted heart potentially via increased connexin43 expression and arteriogenesis.
abstract: Granulocyte colony-stimulating factor (G-CSF), alone or in combination with stem cell factor (SCF), can improve hemodynamic cardiac function after myocardial infarction. Apart from impairing the pump function, myocardial infarction causes an enhanced vulnerability to ventricular arrhythmias. Therefore, we investigated the electrophysiological effects of G-CSF/SCF and the underlying cellular events in a murine infarction model. G-CSF/SCF improved cardiac output after myocardial infarction. Although G-CSF/SCF led to a twofold increased, potentially proarrhythmic homing of bone marrow (BM)-derived cells to the area of infarction, <1% of these cells adopted a cardial phenotype. Inducibility of ventricular tachycardias during programmed stimulation was reduced 5 wk after G-CSF/SCF treatment. G-CSF/SCF increased cardiomyocyte diameter, arteriogenesis, and expression of connexin43 in the border zone of the infarction. An enhanced expression of the G-CSF receptor demonstrated in cardiomyocytes and other cell types of the infarcted myocardium indicates a sensitization of the heart to direct influences of this cytokine. In addition to paracrine effects potentially caused by the increased homing of BM-derived cells, these might contribute to the therapeutic effects of G-CSF.
authors.affiliation: Department of Cardiology and Angiology, University of Münster, 48129 Münster, Germany.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Kuhlmann
authors.forename: Paulus
authors.initials: P
authors.lastname: Kirchhof
authors.forename: Rainer
authors.initials: R
authors.lastname: Klocke
authors.forename: Lekbira
authors.initials: L
authors.lastname: Hasib
authors.forename: Jörg
authors.initials: J
authors.lastname: Stypmann
authors.forename: Larissa
authors.initials: L
authors.lastname: Fabritz
authors.forename: Matthias
authors.initials: M
authors.lastname: Stelljes
authors.forename: Wen
authors.initials: W
authors.lastname: Tian
authors.forename: Melanie
authors.initials: M
authors.lastname: Zwiener
authors.forename: Marcus
authors.initials: M
authors.lastname: Mueller
authors.forename: Joachim
authors.initials: J
authors.lastname: Kienast
authors.forename: Günter
authors.initials: G
authors.lastname: Breithardt
authors.forename: Sigrid
authors.initials: S
authors.lastname: Nikol
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000517:prevention & control*; D016026:Bone Marrow Transplantation; D002302:Cardiac Output / Q000187:drug effects; D018031:Connexin 43 / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006321:Heart / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D019089:Stem Cell Factor / Q000494:pharmacology*; D018487:Ventricular Dysfunction, Left / Q000378:metabolism / Q000503:physiopathology
chemical_list: D018031:Connexin 43; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D019089:Stem Cell Factor; D016179:Granulocyte Colony-Stimulating Factor