G-CSF/SCF reduces inducible arrhythmias in the infarcted heart potentially via increased connexin43 expression and arteriogenesis.
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.
Kuhlmann
Michael T
MT
Department of Cardiology and Angiology, University of Münster, 48129 Münster, Germany.
Kirchhof
Paulus
P
Klocke
Rainer
R
Hasib
Lekbira
L
Stypmann
Jörg
J
Fabritz
Larissa
L
Stelljes
Matthias
M
Tian
Wen
W
Zwiener
Melanie
M
Mueller
Marcus
M
Kienast
Joachim
J
Breithardt
Günter
G
Nikol
Sigrid
S
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
D018031:Connexin 43; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D019089:Stem Cell Factor; D016179:Granulocyte Colony-Stimulating Factor