Abstract 8567: Combination of Active Targeting Erythropoietin-Liposome with Sialyl Lewis X and G-CSF, is Markedly Protective against Ischemia Reperfusion Injury via EPCs Mobilization and Upregulation of p-Akt and p-ERK
Purpose: We previously reported that erythropoietin(EPO)-containing nano-size liposome with Sialyl Lewis X (SLX) and G-CSF prevent cardiac remodeling and improve cardiac function, respectively. Then we hypothesized that combination of EPO-liposome with SLX and G-CSF might be more protective against ischemia reperfusion injury than EPO-liposome with SLX or G-CSF alone.
Methods: Japanese white rabbits (n=40) were subjected to 30-minute coronary occlusion followed by 14 days of reperfusion. Rabbits were administered saline (control group, i.v., n=10), G-CSF (G group, 10μ g/kg/day, i.c., for 5days, n=10), EPO-liposome with SLX (LE group, i.v., 5000IU/ml of EPO, 1ml, n=10), G-CSF + EPO-liposome with SLX (LE+G group, n=10) after reperfusion. Myocardial infarct size was calculated as a percentage of the risk area of the left ventricle. Western blot-analysis examined phosphorylation of Akt and ERK, and expression of E- and P-selectin in the ischemic myocardium at 14days of reperfusion. We also performed fluorescence-activated cell sorter (FACS) analysis of endothelial progenitor cells (EPCs) to evaluate CD34+/CXCR4+ cell mobilization at 7 days after reperfusion.
Results: The infarct size was significantly smaller in the LE+G group (14.0±2.5%) than in the control group (29.0±5.4%), G group (20.3±5.6%) or LE group (18.7±3.7%). Western blot-analysis showed a higher expression of phosphorylated(p)-Akt and p-ERK and expression of E- and P-selectin in the infarct area of the LE+G group than the others. Serum SDF-1 level at 2 days after reperfusion was higher in the G group and the LE+G group than in the Control group or the LE group. The percentages of CD34+/CXCR4+ cells among total peripheral blood mononuclear cells of G group and LE+G group were higher than the others.
Conclusions: Combination of post-infarct treatment with G-CSF and EPO-liposome with SLX markedly reduced the infarct size via EPCs mobilization and upregulation of p-Akt and p-ERK in the ischemic myocardium. This combination therapy may provide a new strategy for the treatment of myocardial infarction.
- © 2011 by American Heart Association, Inc.