Abstract 10291: An Active Targeting Drug Delivery System, a Nano-Size Liposome with Sialyl Lewis X, is a Promising Protective Tool against Ischemia Reperfusion Injury
Purpose: It has been reported that erythropoietin(EPO) prevents cardiac remodeling and improves cardiac function via activation of prosurvival signals and angiogenesis. However, an effective dose of EPO is too high to use clinically. Therefore, we hypothesized that an EPO-containing liposome composed of lipid and ganglioside with Sialyl Lewis X (SLX), which binds with E-selectin expressed in the infarct area, might be protective against ischemia reperfusion injury through an active targeting drug delivery system to the infarcted heart.
Methods: We confirmed using a fluorescent substance Cy5.5-containing liposome(100 nm size) with SLX that liposome with SLX administrated intravenously immediately after myocardial infarction can selectively be accumulated in the infarct area of the myocardium (n=5). Then, in Japanese white rabbits, myocardial infarction was induced by 30 min of ischemia and 14 days of reperfusion. Rabbits were intravenously injected saline (control group, n=10), EPO free-liposome with SLX (L group, n=10) and EPO-containing liposome with SLX (L-EPO group, 1ml, 5000IU/ml EPO, n=10) immediately after reperfusion. Myocardial infarct size was calculated as a percentage of the risk area of the left ventricle. In another rabbits, western blot-analysis was performed to examine phosphorylation of Akt and ERK and upregulation of EPO recepter. We also perfomed immunohistochemical analysis using monoclonal mouse anti-human CD31 antibody.
Results: The infarct size was significantly smaller in the L-EPO group (18.7±3.7%) than in the control group (29.0±5.4%) or in the L group (26.2±3.3%). Western blot-analysis showed a higher expression of phosphorylated(p)-Akt, p-ERK and upregulation of EPO recepter in the infarct area in the L-EPO group than in the control group. The density of the CD31-positive microvessels was clearly greater in the border zone of L-EPO group than the other groups.
Conclusions: EPO-containing liposome with SLX selectively accumulated in the infarct area and reduced the infarct size via upregulation of EPO receptor, p-Akt, p-ERK and acceleration of angiogenesis in the ischemic myocardium. EPO-containing nano-size liposome with SLX may be a promising strategy for the treatment of acute myocardial infarction.
- © 2010 by American Heart Association, Inc.