Darbepoetin improves endothelial function and increases circulating endothelial progenitor cell number in patients with coronary artery disease

Background Atherosclerosis is a progressive disease characterised in part by an imbalance of endothelial decline and endothelial repair. Erythropoietin has been connected to vasculoprotective effects such as enhanced nitric oxide production in endothelial cells and mobilisation of endothelial progenitor cells (EPC). Objective To determine the effect of erythropoietin on endothelial function and EPC mobilisation in humans with atherosclerosis. Design A prospective single-blind monocentric study of 20 patients randomly assigned to the test drug or placebo treatment over 4 weeks. Methods 20 Patients with stable coronary artery disease receiving optimal medical treatment with either weekly subcutaneous injections of saline (placebo) or the recombinant erythropoietin darbepoetin (60 mu g/injection) over 3 consecutive weeks. At the initial and final visits, flow mediated dilatation (FMD) was determined by ultrasound. The number of EPC was determined as the number of CD34/CD133 positive mononuclear cells in peripheral blood. Results Treatment with darbepoetin resulted in a significantly improved FMD in each patient, whereas no difference was seen in placebo-treated patients. The FMD of darbepoetin-treated patients increased by 7.5 +/- 1.64%. Additionally, an increase in peripheral blood EPC of 50 +/- 24% was seen. Conclusion Darbepoetin given in addition to optimal medical treatment resulted in a significantly improved endothelial function in patients with coronary artery disease, indicating a promising new atheroprotective treatment option.