Deficiency of signals mediated by erythropoietin receptors in non-hematopoietic lieage deteriorates survival of cardiomyocytes after myocardial ischemia and reperfusion

Abstract Recent studies have suggested that the administration of erythropoietin (EPO) elicits cardio-protective effects in myocardial ischemia and reperfusion (I/R). We investigated whether endogenous EPO signals mediated by EPO receptors (EPOR) expressed in the non-hematopoietic lineage play a role in the protection against I/R injury using transgene-rescued EPOR null mutant mice (RESCUE), which express EPOR exclusively in the hematopoietic lineage. Left coronary artery was occluded for 30 minutes and then reperfused.The infarct size (% area at risk) was assessed 24 hours after I/R by triphenyltetrazolium chloride staining.The cardiac function and structure were evaluated by echocardiography 3 weeks after I/R. The hematocrit, cardiac structure and function were similar in RESCUE and wild-type (WT) mice in the baseline condition. The infarct size in RESCUE (n = 8) was larger than that in WT (n = 7) (52 ± 4 vs 39 ± 4 %; p