Bone marrow-derived CXCR4+ cells mobilized by macrophage colony-stimulating factor participate in the reduction of infarct area and improvement of cardiac remodeling after myocardial infarction in mice

Hajime Morimoto, Masafumi Takahashi, Yuji Shiba, Atsushi Izawa, Hirohiko Ise, Minoru Hongo, Kiyohiko Hatake, Kazuo Motoyoshi, Uichi Ikeda

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33 Citations (Scopus)

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 (α-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.

Original languageEnglish
Pages (from-to)755-766
Number of pages12
JournalAmerican Journal of Pathology
Volume171
Issue number3
DOIs
Publication statusPublished - Sep 2007

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

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