Macrophage Colony-Stimulating Factor Treatment After Myocardial Infarction Attenuates Left Ventricular Dysfunction by Accelerating Infarct Repair Original Research Article

Objectives We aimed to determine the effects of macrophage colony-stimulating factor (M-CSF) and granulocyte colony-stimulating factor (G-CSF) treatment on both the repair process and ventricular function after myocardial infarction (MI). Background The M-CSF and G-CSF have multiple potential effects on cells involved in wound repair. Methods Myocardial infarction was induced by 45- or 90-min coronary occlusion and reperfusion in rats with or without subsequent injection of M-CSF (106 IU/kg/day) or G-CSF (50 μg/kg/day) for five days. We examined histology and messenger ribonucleic acid (mRNA), and assessed left ventricular function in situ using a conductance catheter. Results Five days after MI, M-CSF increased the number of ED-1–positive cells, mRNA levels of transforming growth factor-β-1, collagen I and III, and collagen fibers within the infarct. Fourteen days after MI, induced by 45-min ischemia, left ventricular end-systolic elastance (Ees) was reduced (1,191 ± 87 mm Hg/ml vs. 1,812 ± 150 mm Hg/ml) and both isovolumic relaxation time constant (τ) (11.9 ± 0.9 ms vs. 8.5 ± 0.4 ms) and left ventricular end-diastolic volume (LVEDV) (0.225 ± 0.014 ml vs. 0.172 ± 0.011 ml) increased versus sham-operated rats. These alterations after MI were attenuated by M-CSF (Ees = 1,650 ± 146, τ = 9.7 ± 0.7, LVEDV = 0.199 ± 0.012) but not by G-CSF. This beneficial effect of M-CSF on Ees was also detected in hearts with MI induced by 90-min ischemia. Furthermore, M-CSF increased collagen content within infarcts and reduced the proportion of thin collagen fibers 14 days after MI. The Ees significantly correlated with infarct collagen content. Nevertheless, neither M-CSF nor G-CSF modified infarct size. Conclusions The M-CSF treatment attenuates deterioration of left ventricular function after MI by accelerating infarct repair.