Abstract 3020: Cardioprotective Effects of Exogenous Erythropoietin in Pressure Overload-Induced Left Ventricular Dysfunction in Mice
Background: Erythropoietin (Epo) receptors (EpoRs) are expressed not only in the bone marrow but also in the heart. We have recently demonstrated that endogenous Epo-EpoR system plays an important protective role in pressure overload-induced left ventricular (LV) dysfunction in mice. In the present study, we tested our hypothesis that exogenous Epo also plays a protective role against pressure overload-induced LV dysfunction in vivo from a clinical point of view.
Methods and Results: C57BL6/J mice were subjected to transverse aortic constriction (TAC) (n=40) or sham operation (n=5). The animals with TAC were randomly assigned to the treatment with vehicle (TAC, n=21) or recombinant human Epo (2000 U/kg, twice a week subcutaneously) (TAC-Epo, n=19) at 24 hours after the surgery. During the 8-week treatment period, the survival rate of the TAC-Epo group was significantly better compared with that of the TAC group (82 vs. 47%, P<0.05). Post-mortem examination revealed severe pulmonary congestion in most of the animals that died within 8 weeks after the initiation of the treatment in both groups. Treatment with Epo resulted in a significant increase in hematocrit as compared with the sham and TAC groups (69 vs. 43 and 45%, both P<0.001). The ratio of LV weight to body weight was significantly increased in the TAC and TAC-Epo groups compared with the sham group (5.5 and 5.3, vs. 3.0 mg/g, both P<0.001), whereas there was no significant difference in the ratio between the TAC and the TAC-Epo groups. Echocardiography at 8-week of the treatment revealed that both LV end-diastolic (LVEDD) and end-systolic diameters (LVESD) were significantly increased (LVEDD 4.2 vs. 3.6 and 3.7 mm, LVESD 3.0 vs. 2.0, 2.2mm, both P<0.05) and LV fractional shortening was significantly decreased (28.3 vs. 43.7 and 40.6%, P<0.05) in the TAC group compared with those in the sham and the TAC-Epo groups. Cardiac catheterization performed at 8-week of the treatment demonstrated that both LV +dP/dt max and LV −dP/dt min tended to be improved in the TAC-Epo group as compared with the TAC group (P=0.08 and 0.07, respectively).
Conclusion: These results suggest that exogenous erythropoietin exerts cardioprotective effects against pressure overload-induced dysfunction in mice in vivo.