Beneficial and ominous aspects of the pleiotropic action of erythropoietin.

The primary function of the glycoprotein hormone erythropoietin (Epo) is to promote red cell production by inhibiting apoptosis of erythrocytic progenitors in hemopoietic tissues. However, functional Epo receptors (Epo-R) have recently been demonstrated in various nonhemopoietic tissues indicating that Epo is a more pleiotropic viability and growth factor. Herein, in vitro and in vivo effects of Epo in the brain and the cardiovascular system are reviewed. In addition, the therapeutic impact of Epo in oncology is considered, including the question of whether Epo might promote tumor growth. Convincing evidence is available that Epo acts as a neurotrophic and neuroprotective factor in the brain. Epo prevents neuronal cells from hypoxia-induced and glutamate-induced cell death. Epo-R is expressed by neurons and glia cells in specific regions of the brain. Epo supports the survival of neurons in the ischemic brain. The neuroprotective potential of Epo has already been confirmed in a clinical trial on patients with acute stroke. With respect to the vasculature, Epo acts on both endothelial and smooth muscle cells. Epo promotes angiogenesis and stimulates the production of endothelin and other vasoactive mediators. In addition, Epo-R is expressed by cardiomyocytes. The role of Epo as a myocardial protectant is at the focus of present research. Epo therapy in tumor patients is practiced primarily to maintain the hemoglobin concentration above the transfusion trigger and to reduce fatigue. In addition, increased tumor oxygenation may improve the efficacy of chemotherapy and radiotherapy. However, tumor cells often express Epo-R. Therefore, careful studies are required to fully exclude that recombinant human Epo (rHuEpo) promotes tumor growth.