Cytokine therapy prevents left ventricular remodeling and dysfunction after myocardial infarction through neovascularization.

Pretreatment with a combination of granulocyte colony-stimulating factor (G-CSF) and stem cell factor (SCF) has been reported to attenuate left ventricular (LV) remodeling after acute myocardial infarction (MI). We here examined whether the cytokine treatment started after MI has also beneficial effects. Anterior MI was created in the recipient mice whose bone marrow had been replaced with that of transgenic mice expressing enhanced green fluorescent protein (GFP). We categorized mice into five groups according to the following treatment: 1) saline; 2) administration of G-CSF and SCF from 5 days before MI through 3 days after; 3) administration of G-CSF and SCF for 5 days after MI; 4) administration of G-CSF alone for 5 days after MI; 5) administration of SCF alone for 5 days after MI. All the three treatment groups with G-CSF showed less LV remodeling and improved cardiac function and survival rate after MI. The number of capillaries, which express GFP, was increased and the number of apoptotic cells was decreased in the border area of all the treatment groups with G-CSF. Even if the cytokine treatment is started after MI, it could prevent LV remodeling and dysfunction after MI--at least in part--through an increase in neovascularization and a decrease in apoptosis in the border area.