Narrowing of the arteries due to atherosclerosis may lead to congestive heart failure (CHF). It is advantageous to perform atherosclerosis studies in apolipoprotein E-deficient (Apo E-/-) mice models, which develop atherosclerosis very rapidly in comparison to humans. Darbepoetin is a synthetic erythropoietin analogue and stimulates erythropoiesis. The aim of this study was to explore the effect of 16 weeks of darbepoetin treatment on serum protein profiles in Apo E-/- mice during atherosclerosis progression. Serum proteomic analyses were performed using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) in the darbepoetin-treated and non-treated (control) Apo E-/- mice groups. The protein profiles obtained using three different chips, CM-10 (weak cation exchange), H50 (reversed-phase) and IMAC-30 (immobilized metal affinity capture), were statistically analyzed using the ProteinChip data manager 3.0 program. At the end of 16 weeks of darbepoetin treatment, there was no significant difference in the size and degree of atherosclerotic lesions between the darbepoetin and control mice groups. In contrast, 145 protein/peptide-clustering peaks, >5 kDa, had statistically significant differences in their peak intensities between the darbepoetin and control mice groups (p < 0.05). That the proteonnic profiles of darbepoetin-treated Apo E-/- mice were found to differ from those of the control group indicates a potential beneficial role of darbepoetin in atherosclerosis. Our study contributes to understanding the effects of darbepoetin on protein/peptide expressions during atherosclerosis development. (C) 2009 Elsevier GmbH. All rights reserved.