[Pleiotropic effects of erythropoietin]

Since the isolation and purification of erythropoietin (EPO) in 1977, the essential role of EPO for mature red blood cell production has been well established. The cloning of the EPO gene and production of recombinant human EPO led to the widespread use of EPO in treating patients with anaemia. In addition to stimulating erythropoiesis, EPO has several extrahaematopoietic functions including neuro-, reno- and caridioprotection. EPO receptor (EPOR) expression is also found in endothelial, brain, cardiovascular and other tissues, although at levels considerably lower than that of erythroid progenitor cells. This review discusses the survival and proliferative activity of EPO that extends beyond erythroid progenitor cells. Loss of EpoR expression in mouse models provides evidence for the role of endogenous EPO signalling in nonhaematopoietic tissue during development or for tissue maintenance and/or repair. Determining the extent and distribution of receptor expression provides insights into the potential protective activity of EPO in brain, heart and other nonhaematopoietic tissues. The administration of recombinant EPO reduced brain injury associated with stroke, blunt trauma, and prevented ischaemic injury in the spinal cord. Studies suggest that EPO also protects heart tissues by enhancing angiogenesis, attenuating myocardial ischaemic/reperfusion injury, and attenuating the effects of cytotoxic drugs. EPO protects against ischaemic/reperfusion injury by inhibition of apoptosis and hypoxia, limiting infarct size and preserving myocardium.