The Journal of Experimental Medicine
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Published online 9 January 2006 doi:10.1084/jem.20051151
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 203, Number 1, 87-97
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ARTICLE

G-CSF/SCF reduces inducible arrhythmias in the infarcted heart potentially via increased connexin43 expression and arteriogenesis

Michael T. Kuhlmann1, Paulus Kirchhof1,2, Rainer Klocke1, Lekbira Hasib1, Jörg Stypmann1,2, Larissa Fabritz1,2, Matthias Stelljes3, Wen Tian1, Melanie Zwiener1,2, Marcus Mueller4, Joachim Kienast3, Günter Breithardt1,5, and Sigrid Nikol1

1 Department of Cardiology and Angiology, 2 Interdisciplinary Center for Clinical Research Münster, 3 Department of Medicine/Hematology and Oncology, 4 Department of Neurology, and 5 Leibniz Institute for Arteriosclerosis Research, University of Münster, 48129 Münster, Germany

CORRESPONDENCE Sigrid Nikol: nikol{at}uni-muenster.de

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.


Abbreviations used: BMT, BM transplantation; ECG, electrocardiogram; EGFP, enhanced green fluorescent protein; G-CSF, granulocyte colony-stimulating factor; LAD, left anterior descending coronary artery; MAP, monophasic action potential; SCF, stem cell factor

M.T. Kuhlmann and P. Kirchhof contributed equally to this work.


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