Post‐MI treatment with G‐CSF and EPO‐liposome with SLX repairs infarcted myocardium through EPCs mobilization and activation of prosurvival signals in rabbits

摘要

We investigated whether combination therapy of G‐CSF and erythropoietin (EPO)‐liposome with Siaryl Lewis X (SLX) is more cardioprotective than G‐CSF or EPO‐liposome with SLX alone. For the purpose of generating myocardial infarction (MI), rabbits underwent 30 minutes of coronary occlusion and 14 days of reperfusion. We administered saline (control group, i.v.,), G‐CSF (G group, 10 μg/kg/day × 5 days, i.c., starting at 24 hours after reperfusion), EPO‐liposome with SLX (LE group, i.v., 2500 IU/kg EPO containing liposome with SLX, immediately after reperfusion), and G‐CSF + EPO‐liposome with SLX ( style="fixed-case">LE + G group) to the rabbits. The style="fixed-case">MI size was the smallest in the style="fixed-case">LE+G group (14.7 ± 0.8%), and smaller in the G group (22.4 ± 1.5%) and style="fixed-case">LE group (18.5 ± 1.1%) than in the control group (27.8 ± 1.5%). Compared with the control group, the cardiac function and remodeling of the G, style="fixed-case">LE, and style="fixed-case">LE + G groups were improved, and style="fixed-case">LE + G group tended to show the best improvement. The number of style="fixed-case">CD31‐positive microvessels was the greatest in the style="fixed-case">LE + G group, greater in the G and style="fixed-case">LE groups than in the control group. Higher expressions of phosphorylated (p)‐Akt and p‐ style="fixed-case">ERK were observed in the ischemic area of the style="fixed-case">LE and style="fixed-case">LE + G groups. The number of style="fixed-case">CD34⁺/ style="fixed-case">CXCR4⁺ cells was significantly higher in the G and style="fixed-case">LE + G groups. The cardiac style="fixed-case">SDF‐1 was more expressed in the G and style="fixed-case">LE + G groups. In conclusion, Post‐ style="fixed-case">MI combination therapy with G‐ style="fixed-case">CSF and style="fixed-case">EPO‐liposome with style="fixed-case">SLX is more cardioprotective than G‐ style="fixed-case">CSF or style="fixed-case">EPO‐liposome with style="fixed-case">SLX alone through style="fixed-case">EPCs mobilization, neovascularization, and activation of prosurvival signals.