Search

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 < 0.05).The left ventricular (LV) end-diastolic dimension was significantly increased (5.0 ± 0.2 vs 3.8 ± 0.2 mm; p < 0.01), and the LV fractional shortening was reduced (0.15 ± 0.01 vs 0.26 ± 0.05; p < 0.01) in the RESCUE (n=8) compared with WT (n=6) 3 weeks after I/R. In conclusion, a deficiency of endogenous EPO-EPOR signal in the non-hematopoietic lineage may deteriorate the survival of cardiomyocytes after I/R, and accelerate the development of LV remodeling. The endogenous EPO-EPOR system in the non-hematopoietic lineage may play a crucial role in the protection against I/R injury.