Abstract
The monocyte/macrophage lineage might affect the healing process after myocardial infarction (MI). Because macrophage colony-stimulating factor (M-CSF) stimulates differentiation and proliferation of this lineage, we examined the effect of M-CSF treatment on infarct size and left ventricular (LV) remodeling after MI. MI was induced in C57BL/6J mice by ligation of the left coronary artery. Either recombinant human M-CSF or saline was administered for 5 consecutive days after MI induction. M-CSF treatment significantly reduced the infarct size (P < 0.05) and scar formation (P < 0.05) and improved the LV dysfunction (percent fractional shortening, P < 0.001) after the MI. Immunohistochemistry revealed that M-CSF increased macrophage infiltration (F4/80) and neovascularization (CD31) of the infarct myocardium but did not increase myofibroblast accumulation (alpha-smooth muscle actin). M-CSF mobilized CXCR4(+) cells into peripheral circulation, and the mobilized CXCR4(+) cells were then recruited into the infarct area in which SDF-1 showed marked expression. The CXCR4 antagonist AMD3100 deteriorated the infarction and LV function after the MI in the M-CSF-treated mice. In conclusion, M-CSF reduced infarct area and improved LV remodeling after MI through the recruitment of CXCR4(+) cells into the infarct myocardium by the SDF-1-CXCR4 axis activation; this suggests that the SDF-1-CXCR4 axis is as a potential target for the treatment of MI.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis / physiology
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Benzylamines
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Cell Differentiation / physiology
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Cells, Cultured
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Chemokine CXCL12 / metabolism
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Collagen / metabolism
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Cyclams
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Cytokines / metabolism
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Echocardiography
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Endothelial Cells / cytology
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Endothelial Cells / metabolism
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Granulocyte Colony-Stimulating Factor / metabolism
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Heterocyclic Compounds / metabolism
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Humans
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Macrophage Colony-Stimulating Factor / metabolism*
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Macrophages / cytology
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Macrophages / metabolism*
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Male
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Mice
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Mice, Inbred C57BL
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Myocardial Infarction* / metabolism
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Myocardial Infarction* / pathology
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Myocardium / cytology
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Myocardium / metabolism
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Myocardium / pathology
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Neovascularization, Physiologic
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Receptor, Macrophage Colony-Stimulating Factor / genetics
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Receptor, Macrophage Colony-Stimulating Factor / metabolism
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Receptors, CXCR4 / antagonists & inhibitors
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Receptors, CXCR4 / genetics
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Receptors, CXCR4 / metabolism*
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Receptors, Granulocyte Colony-Stimulating Factor / genetics
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Receptors, Granulocyte Colony-Stimulating Factor / metabolism
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Transforming Growth Factor beta1 / metabolism
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Ventricular Remodeling / physiology*
Substances
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Benzylamines
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CXCR4 protein, mouse
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Chemokine CXCL12
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Cxcl12 protein, mouse
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Cyclams
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Cytokines
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Heterocyclic Compounds
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Receptors, CXCR4
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Receptors, Granulocyte Colony-Stimulating Factor
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Transforming Growth Factor beta1
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Granulocyte Colony-Stimulating Factor
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Macrophage Colony-Stimulating Factor
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Collagen
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Receptor, Macrophage Colony-Stimulating Factor
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