Abstract 614: Neovascularisation after Erythropoietin Treatment in Heart Failure is Associated with Increased Myocardial Homing and Vascular Incorporation of Endothelial Progenitor Cells
Background: The hematopoietic hormone erythropoietin (EPO) has been implicated in myocardial neovascularisation in heart failure. The underlying mechanism is unknown and might involve endothelial progenitor cells (EPC). Therefore, we evaluated the role of bone marrow derived EPC in EPO induced neovascularisation.
Methods: Bone marrow of male Fischer (f344) rats was replaced by bone marrow cells that ubiquitously expressed human placental alkaline phosphatase (hPAP). Hereafter, heart failure was induced by myocardial infarction (MI), and rats were randomly allocated to EPO (MI-EPO, n=12) or vehicle (MI, n=12, sham n=9) treatment starting three weeks after MI. After 9 weeks, the incorporation of EPC into the myocardial vasculature was evaluated by immunohistochemistry (hPAP+ and RECA (his52)+). The effects of treatment were further characterised by evaluating cardiac function, circulating EPC, capillary density and myocardial expression of vascular endothelial growth factor (VEGF).
Results: EPO significantly improved cardiac function (p<0.02) and restored capillary density to sham levels ( p<0.02 v.s. MI). EPO treatment resulted in a 3-fold increase in circulating EPC (p<0.03), and induced specific homing of EPC to the myocardium reflected by a 70 % increase in bone marrow derived endothelial cells (BMDEC) (p<0.02, figure 1⇓), and a significantly increased BMDEC / total BMDC ratio (p<0.001). The incorporation of EPC was associated with increased myocardial expression of VEGF, suggesting a paracrine mechanism of neovascularisation.
Conclusions: EPO-induced neovascularisation is associated with increased myocardial homing and vascular incorporation of EPC.