Erythropoietin stimulates normal endothelial progenitor cell-mediated endothelial turnover, but attributes to neovascularization only in the presence of local ischemia

B. Daan Westenbrink*, Hisko Oeseburg, Lennaert Kleijn, Pim van der Harst, Anne M. S. Belonje, Adriaan A. Voors, Regien G. Schoemaker, Rudolf A. De Boer, Dirk J. van Veldhuisen, Wiek H. van Gilst

*Corresponding author for this work

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Abstract

Purpose We aimed to evaluate whether ischemia is required for erythropoietin (EPO) induced stimulation of endothelial progenitor cells (EPCs) and their related effects on endothelial and cardiac function.

Methods Bone marrow of rats was replaced by transgenic cells to allow tracking of EPCs. Ischemic heart failure was induced by left coronary artery ligation to induce myocardial infarction (MI) and control rats received a sham procedure. Three weeks after surgery, rats were randomized to receive EPO (darbepoetin alfa 40 mu g/kg per 3 weeks) or vehicle and were sacrificed 9 weeks after surgery.

Results In all treated groups, EPO significantly increased circulating EPCs and their incorporation into the endothelium of the ischemic and non-ischemic hearts as well as in the control organs; kidney and liver. This was associated with significantly improved endothelial function, which was strongly correlated with circulating EPCs (R=0.7, p

Conclusions In general, EPO stimulates normal endothelial progenitor cell-mediated endothelial turnover, but improves cardiac microvascularization and function only in the presence of ischemia.

Original languageEnglish
Pages (from-to)265-274
Number of pages10
JournalCardiovascular Drugs and Therapy
Volume22
Issue number4
DOIs
Publication statusPublished - Aug-2008

Keywords

  • erythropoietin
  • endothelial function
  • heart failure
  • endothelial progenitor cells
  • IMPROVES CARDIAC-FUNCTION
  • DOXORUBICIN-INDUCED CARDIOMYOPATHY
  • NITRIC-OXIDE SYNTHASE
  • CHRONIC HEART-FAILURE
  • DARBEPOETIN-ALPHA
  • MYOCARDIAL-INFARCTION
  • BONE-MARROW
  • DYSFUNCTION
  • RATS
  • EXPRESSION

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