Hormones – Cytokines – Signaling
Kidney International (2003) 64, 1648–1652; doi:10.1046/j.1523-1755.2003.00279.x
Endothelial progenitor cell proliferation and differentiation is regulated by erythropoietin Rapid Communication
Ferdinand H Bahlmann1, Kirsten Degroot1, Thorsten Duckert, Eva Niemczyk, Elisabeth Bahlmann, Sascha M Boehm, Hermann Haller and Danilo Fliser
Division of Nephrology, Department of Internal Medicine, Hanover Medical School, Hanover, Germany; and Phenos GmbH, Hanover, Germany
Correspondence: Ferdinand H. Bahlmann, M.D., Department of Internal Medicine, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany. E-mail: Bahlmann.Ferdinand@MH-Hannover.de
1Dr. Bahlman and Dr. DeGroot contributed equally to the study.
Received 3 April 2003; Revised 13 May 2003; Accepted 1 July 2003.
Abstract
Endothelial progenitor cell proliferation and differentiation is regulated by erythropoietin.
Background
Circulating bone marrow–derived endothelial progenitor cells (EPCs) promote vascular reparative processes. In humans, their number correlate with endothelial function and cardiovascular risk. We tested the hypothesis that darbepoetin alfa [i.e., a recombinant analogue of the cytokine erythropoietin (EPO)] stimulates proliferation and differentiation of EPCs.
Methods
We assessed CD34+ circulating stem cells (cSCs) in whole blood using flow cytometry and, in addition, proliferation/differentiation of EPCs in an in-vitro assay during 6 weeks of a standard darbepoetin therapy in eight patients with renal anemia.
Results
Darbepoetin treatment caused a significant increase in the number of CD34+ cSCs (week 2, 193%
46%; and week 6, 298% 90%; P < 0.05 vs. baseline). In addition, darbepoetin markedly increased the number of functionally active EPCs (week 2, 256% 48%; and week 6, 299% 59%; both P < 0.01 vs. baseline). The effect of darbepoetin on functional activity of EPCs assessed in a tube formation assay was dose dependent. Administration of darbepoietin caused activation of protein kinase B (Akt) in cultured EPCs.
Conclusion
A standard treatment with darbepoetin markedly enhances EPC proliferation and differentiation in renal patients. The use of recombinant EPO analogues may be a novel and safe therapeutic approach in patients with vascular pathology.
Keywords:
angiogenesis, darbepoetin, endothelium, erythropoetin, endothelial progenitor cells, vasculogenesis
