Beyond erythropoiesis: the anti-inflammatory effects of erythropoietin.

Erythropoietin (EPO) is a 30.4-kDa glycoprotein essential for red blood cell production. In adults, EPO is produced primarily in the kidney via an oxygen-sensing mechanism and stimulates erythroid progenitors in the bonemarrow to increase red blood cell mass. In addition to its role in erythropoiesis, EPO has been shown to protect against ischemic injury in several organs including the heart. In various animal models, administration of EPO reduces infarct size and improves cardiac function following myocardial ischemia and reperfusion (I/R). The protective effects have been observed regardless of whether EPOwas administered before ischemia, at the onset of ischemia, or at reperfusion [1,2]. The protective effects of EPO are also seen in chronic models of myocardial infarction (MI). In this regard, treatment of EPO before or immediately after coronary artery ligation decreases cardiac remodeling and improves myocardial function. Interestingly, a single dose of EPO (3000 IU/kg, i.p.) immediately after induction of MI improved cardiac function measured 8 weeks later. The therapeutic relevance of EPO was further demonstrated by van der Meer et al., who showed that EPO treatment started 3weeks afterMI improved cardiac function in a ratmodel of heart failure [3]. Consistent with this finding, in a report in this issue of Cardiovascular Research, EPO was started 6 weeks after induction of MI when heart failure was fully established in mice. Four weeks of EPO treatment diminished left ventricular (LV) dilatation and improved cardiac function [4].