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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org

The role of CXCR4/SDF-1, CD117/SCF, and c-met/HGF chemokine signalling in the mobilization of progenitor cells and the parameters of the left ventricular function, remodelling, and myocardial perfusion following acute myocardial infarction

Wojciech Wojakowski1,4,*, Magda Kucia2, Krzysztof Milewski3, Boguslaw Machalinski5, Maciej Halasa5, Pawel Buszman3, Piotr Klimeczek6, Maciej Kazmierski1, Mieczyslaw Pasowicz6, Mariusz Z. Ratajczak2 and Michal Tendera1,4

1 Third Division of Cardiology, Silesian School of Medicine, 45-47 Ziolowa Street, 40-635 Katowice, Poland
2 Stem Cell Biology Program at James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA
3 Acute Coronary Care Unit, Silesian School of Medicine, Katowice, Poland
4 European Vascular Genomics Network
5 Department of General Pathology Pomeraniam Medical University, Szczecin, Poland
6 Center for Diagnosis and Rehabilitation of Heart and Lung Diseases, John Paul II Hospital, Kraków, Poland

* Corresponding author. Tel: +48 60 4188669; fax: +48 32 2523930. E-mail address: wojwoj{at}mp.pl

Chemokines and their receptors induce the qualitative and quantitative changes of the pool of bone marrow-derived and resident cardiac stem/progenitor cells, which in turn can modulate myocardial recovery after myocardial infarction (MI). Primary role of the chemokines, such as stromal cell-derived factor-1 (SDF-1), stem cell factor (SCF), hepatocyte growth factor (HGF) and leukaemia inhibitory factor (LIF) is the mobilization and homing of the bone marrow-derived stem/progenitor cells to the infarcted myocardium. In the setting of the acute MI there is an increased expression of SDF-1, HGF, LIF in the peri-infarct zone. The most important chemokine–chemokine receptor axis is SDF-1/CXCR4 which is significantly upregulated during acute MI. It corresponds with the significant mobilization of cells expressing cardiac and endothelial markers, which also express the chemokine receptors CXCR4, c-met, CD117 and leukemia inhibitory factor receptor. Specific population of small non-haematopoietic cells expressing the CXCR4 receptor was identified, which have the capability of cardiogenic differentiation. The mobilization of stem/progenitor cells expressing the receptors for chemoattractant cytokines is significantly correlated with the improvement of left ventricular ejection fraction (LVEF) and remodelling in 1-year follow-up after the acute MI. Patients with reduced LVEF after MI have also impaired mobilization of the stem/progenitor cells. The number of circulating cells is inversely correlated with the infarct area and positively with myocardial perfusion. Also the migratory response of the endothelial progenitor cells (EPCs) to the SDF-1 gradient is positively correlated with their capability to improve the perfusion and is one of the factors that seem to determine the outcome of the progenitor cell-based therapy after acute MI.

Key Words: Stem cells • Acute coronary syndromes • Chemokines • Mobilization • Endothelial progenitor cells


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