Chapter 11

Effects of Erythropoietin on Blood Vessels and the Heart

Wolfgang Jelkmann and Steve Elliott


Erythropoietin (EPO) stimulates erythropoiesis through binding to and activation of homodimeric receptors, comprised of two ~59 kDa transmembrane proteins (EPO-R). Preclinical studies purported pleiotropic cytoprotective roles for the EPO/EPO-R system in tissues and organs, and the potential benefits of erythropoiesisstimulating agents (ESAs) for cardiovascular diseases are a focus of current research. This article summarizes putative actions of ESAs in the cardiovascular system, with emphasis on the human responses. The potential for EPO-mediated mobilization of stem cells into the blood stream has attracted wide interest because of the possibility that ESAs may promote the neovascularization of ischemic tissues. Supporting the possibility, EPO-R mRNA is detectable in vascular endothelium, and EPO has been reported to stimulate angiogenesis in some preclinical models. However, in most such studies very high concentrations of EPO were applied. Moreover, recent well-designed studies have failed to show direct effects of ESAs on endothelial cells. By use of a specific anti-EPO-R antibody very little EPO-R protein was detected on immunoblots of extracts from normal cardiovascular tissues. While in preclinical studies high-dosed ESAs reduced the myocardial infarct volume and improved contractile properties following ischemia, human placebo-controlled clinical trials failed to demonstrate clear beneficial effects of ESAs in patients with coronary syndrome or myocardial infarct. ESA therapy is currently used to prevent red blood cell transfusions in anemic patients with chronic kidney disease or chemotherapy for cancer and is being explored as an anti-anemia treatment in patients with heart disease. However, because blood viscosity increases and blood pressure may rise with hematocrit, hemoglobin concentrations should not be raised above indicated levels.

Total Pages: 180-204 (25)

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