Abstract 10906: Active Cardiac Targeting Delivery of Erythropoietin by Liposomes Repairs Infarcted Myocardium Through Activation of Prosurvival Signals and Angiogenesis in Rabbits
Backgrounds: Erythropoietin (EPO) exerts cardioprotection but causes side effects such as polycytemia. Therefore, cardiac targeting delivery system of EPO without side effects is required. We investigated whether a cardiac targeting nano-sized liposomal EPO reduces the infarct size and improves cardiac remodeling and function after myocardial infarction.
Methods: Using a fluorescent substance Cy5.5-containing liposome (100 nm size) with Sialyl Lewis X (SLX), we confirmed that liposome with SLX administrated intravenously immediately after myocardial infarction can selectively be accumulated in the infarct area of the myocardium . Then we prepared EPO-encapsulated liposome with SLX which selectively combines with E- and P-selectins in the infarcted cardiac tissues. Rabbits (male, 2 kg) underwent 30 min of coronary occlusion and 2, 14 days of reperfusion. Rabbits then received intravenous injections of saline (Saline group), liposome without EPO (liposome group) and 5000 IU/kg of EPO-encapsulated liposome (EPO-liposome group) immediately after reperfusion. Myocardial infarct size, fibrosis areas, cardiac function, the number of microvessels and prosurvival signals in the myocardium after myocardial infarction were obtained.
Results: The infarct size, LV dimensions, and cardiac fibrosis areas were significantly smaller in the EPO-liposome group than in the liposome or Saline group at 14 days after myocardial infarction. The number of CD31-positive microvessels was significantly greater in the EPO-liposome group than in the others. Western blotting revealed expression levels of EPO-receptors, E-selectin, P-selectin, phosphorylated (p)-Akt, p-ERK, p-Stat3, VEGF and pro-matrix metalloproteinase (MMP)-1 were all markedly increased in the ischemic areas of hearts from the EPO-liposome group.
Conclusions: The EPO-encapsulated liposome with SLX selectively accumulated in the infarct area, reduced the myocardial infarct size and improved LV remodeling and function without side effects through activation of pro-survival signals and by exerting antifibrotic and angiogenic effects. EPO-encapsulated liposome with SLX may be a promising strategy for active targeting treatment of acute myocardial infarction.
- © 2012 by American Heart Association, Inc.