Changes in vascular endothelial growth factor, angiopoietins, and Tie-2 levels with G-CSF stimulation in healthy donors

The roles of vascular endothelial growth factor (VEGF), Tie-2, and angiopoietins in the mobilization of the hematopoietic stem cells (HSCs) in humans are not yet clearly understood. In order to elucidate mechanisms of HSC mobilization from their niches, we aimed to investigate the effects of mobilization with granulocyte colony-stimulating factor to the levels of VEGF, Tie-2, and angiopoietins 1 and 2 in the allogeneic HSC transplantation donors. Soluble VEGF, Tie-2, angiopoietin 1 and angiopoietin 2 levels were studied in 20 healthy allogeneic HSC transplantation donors before (from peripheral blood) and 5 days after mobilization (from apheresis material). Mean VEGF level in the postmobilization apheresis sample was significantly higher compared to baseline premobilization peripheral blood (t test, p < 0.001). In contrast, mean Tie-2 level in the postmobilization aphaeresis sample was significantly lower compared to baseline premobilization peripheral blood (t test, p = 0.01). Angiopoietin 1 and angiopoietin 2 levels did not differ between baseline and postmobilization samples. A significant rise in VEGF level after mobilization suggests stimulation of the angiogenesis. A significant fall in Tie-2 level suggests suppression of the angiopoietin 1/Tie-2 signaling, leading to release of HSC from the hematopoietic niches and mobilization to the peripheral blood.