Short-term intermittent administration of CXCR4 antagonist AMD3100 facilitates myocardial repair in experimental myocardial infarction.

The binding of the stromal cell-derived factor-1α (SDF-1α) to the cysteine (C)-X-C motif chemokine receptor 4 (CXCR4) has emerged as a key signal for stem and progenitor cells trafficking to the circulation from the bone marrow. Our aim was to investigate the role of daily intermittent administration of AMD3100 (a specific reversible CXCR4 receptor antagonist) during the healing process after myocardial infarction (MI). Wistar rats were subjected to MI and AMD3100 was injected intraperitoneally after surgery. SDF-1α mRNA expression was measured by real-time polymerase chain reaction. Histology changes were analyzed with immunofluorescence, Masson's trichrome staining, and wheat germ agglutinin. The number of leukocytes in peripheral blood was measured by complete blood cell count analysis. The activities of matrix metalloproteinase-2/9 (MMP-2/9) were determined by gelatin zymography. The expression level of SDF-1α mRNA in the infarcted tissue was enhanced rapidly (6 h), peaked at 24 h, and then declined to the normal level at 7 days post-MI. AMD3100 further enhanced the increase of SDF-1α in infarct area. Increased leukocytes were observed in AMD3100-treated groups. The mobilization of c-kit(+) stem/progenitor cells and enhanced neovascularization were augmented by AMD3100. Additionally, AMD3100 improved ventricular remodeling, which was revealed by the decrease of infarct size, viable cardiomyocyte cross-sectional area and left ventricle (LV) expansion index, and the increase of LV free wall thickness. The activities of MMP-2/9 were up-regulated by AMD3100. In conclusion, short-term intermittent administration of AMD3100 could accelerate the wound healing process in experimental MI and be a potential therapy for the treatment of MI.