Objectives: Erythropoietin (EPO) administration in acute stroke revealed clinically significant neuroprotection. Recently, animal experiments showed superior cardiac function in EPO treated animals subjected to myocardial infarction. While in cell lines and rodent myocardium the EPO receptor had been described, for the adult human myocardium there is no such report to date. Therefore, we investigated adult human cardiac tissue for the presence of the EPO receptor and to identify the cell types expressing the EPO receptor.
Methods: After approval by the Institutional Review Board, ventricular tissue from the muscular septum obstructing the left ventricular out flow track (Morrow procedure) or right atrial tissue from the site of the venous canulation was obtained (n=4 per group). Additional samples were obtained before and after cardio-pulmonary bypass (CPB). Tissue samples were investigated for the EPO receptor and the transcription factor HIF-1alpha by RT-PCR, Western blot and (double) immunohistochemistry.
Results: We show for the first time that EPO receptor mRNA and protein is indeed expressed in adult human atrial and ventricular tissue. Cardiac EPO receptor positive cells were the cardiomyocytes of atrial and ventricular origin as well as vascular endothelial cells. After CPB HIF-1alpha was decreased due to the improved perfusion following CABG, and the EPO-receptor was markedly upregulated.
Conclusion: EPO receptor is expressed in the human heart. These findings encourage to investigate the potential of EPO-induced myocardial cytoprotection in humans. The EPO receptor in the heart appears not to be regulated by HIF-1alpha.
