Erythropoietin regulates endothelial progenitor cells.
Circulating bone marrow-derived endothelial progenitor cells (EPCs) promote vascular reparative processes and neoangiogenesis, and their number in peripheral blood correlates with endothelial function and cardiovascular risk. We tested the hypothesis that the cytokine erythropoietin (EPO) stimulates EPCs in humans. We studied 11 patients with renal anemia and 4 healthy subjects who received standard doses of recombinant human EPO (rhEPO). Treatment with rhEPO caused a significant mobilization of CD34(+)/CD45(+) circulating progenitor cells in peripheral blood (measured by flow cytometry), and increased the number of functionally active EPCs (measured by in vitro assay) in patients (week 2, 312% +/- 31%; week 8, 308% +/- 40%; both P <.01 versus baseline) as well as in healthy subjects (week 8, 194% +/- 15%; P <.05 versus baseline). The effect on EPCs was already observed with an rhEPO dose of about 30 IU/kg per week. Administration of rhEPO increased the number of functionally active EPCs by differentiation in vitro in a dose-dependent manner, assessed in cell culture and by tube formation assay. Furthermore, rhEPO activates the Akt protein kinase pathway in EPCs. Erythropoietin increases the number of functionally active EPCs in humans. Administration of rhEPO or EPO analogs may open new therapeutic strategies in regenerative cardiovascular medicine.
Bahlmann
Ferdinand H
FH
Department of Internal Medicine, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany. bahlmann.ferdinand@mh-hannover.de
De Groot
Kirsten
K
Spandau
Jens-Michael
JM
Landry
Aimee L
AL
Hertel
Barbara
B
Duckert
Thorsten
T
Boehm
Sascha M
SM
Menne
Jan
J
Haller
Hermann
H
Fliser
Danilo
D
D000740:Anemia / Q000097:blood / Q000188:drug therapy / Q000473:pathology; D018952:Antigens, CD34 / Q000378:metabolism; D001772:Blood Cell Count; D016022:Case-Control Studies; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects* / Q000276:immunology; D004921:Erythropoietin / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D007676:Kidney Failure, Chronic / Q000097:blood / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
D018952:Antigens, CD34; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D004921:Erythropoietin