Abstract 236: Heart Failure Remodeling: Local Endogenous Erythropoietin and Erythropoietin Receptor Expression
Erythropoietin (EPO) via erythropoietin receptor (EPOR) maintains myeloid erythropoiesis, however in a failing heart (FH) it seems to exert cytoprotective, antiapoptotic, proangiogenic effects.
Aim: to assess (myocardial) M-EPOR expression and to find out if erythropoietin (M-EPO) is produced in human heart; secondary to elucidate the mechanisms related to M-EPO/M-EPOR expression.
Methods: We used 33 explanted FH, compared to 11 non-failing hearts (NFH). Patients characteristics: left ventricle (LV - EF 22±11%), NTproBNP (5464±4825 pg/ml). Serum variables: iron (62±32ug/dl), ferritin (156±122ng/ml), transferrin receptor (3.8±2.6mg/l), EPO (29.5±44.4mIU/ml), HT (39.8±5.3%), Hb (13.2±1.7g/dl), creatinine clearance (CrCl 68±23 ml/min), Na+ (138±5.4 mmol/l).
Myocardial assesment: M-EPO, M-EPOR, iron storage protein - ferritin (M-FR), iron acquisition protein transferrin receptor (M-TfR), Iron Regulatory Protein 1 (M-IRP1) - by ELISA - ng/mg protein - expression; myocardial iron load - by Instrumental Neutron Activation Analysis, µg/g.
Results: In FH and NFH M-EPO/M-EPOR expression were detected; M-EPO was elevated in failing LV (in FH vs NFH 4.7±1.6 vs 3.7±1.4, p=0.0346; ng/mg protein), no changes in M-EPOR was found. M-EPO correlated with M-EPOR from both ventricles (LV- left r=0.63, p=0.0002; RV - right r=0.42, p=0.0161). With regard to anemia (by WHO), patients were divided into two subgroups: A+ (n=11) and A- (n=22). In A+ vs A- serum EPO (47±23 vs 28±30 mIU/l, p=0.0473) was higher. In myocardium A+ M-TfR was lower than in A- both LV (136±61 vs 218±134; p=0.0446) and RV (130±92 vs 199±143; p=0.0688), however no differences in M-EPO/M-EPOR/M-FR/M-IRP1 and iron load were found. In LV, A+ subgroup, IRP1 correlation with M-EPO (r=0.79, p=0.0107) and M-EPOR (r=0.76, p=0.0184).
Conclusions: M-EPO/M-EPOR are synthesized locally in human hearts. In failing LV M-EPO synthesis is significantly increased. M-EPO production correlated with M-EPOR expression. M-EPO/EPOR expression is associated with regulatory protein IRP1. The presence of anemia accompanied by high plasma EPO is not connected with modification of myocardial expression: M-EPO/M-EPOR/M-FR/M-IRP1, iron load, except for M-TfR.
- © 2012 by American Heart Association, Inc.