Oxygen affects human endothelial cell proliferation by inactivation of fibroblast growth factors

The fibroblast growth factors (FGF), including endothelial cell growth factor (ECGF)/acidic FGF and basic FGF, are important modulators of endothelial cell replication in vitro and in vivo. Premature infants and adults with lung injuries are often treated with high levels of inspired O2, which can be necessary for survival but potentially injurious to developing lungs and in tissue repair following injury. Human umbilical artery and vein endothelial cells were grown in ECGF- or FGF-supplemented Medium 199 and exposed to ambient levels of O2 from 10 to 95%. Endothelial cell growth, measured by [3H]thymidine incorporation, was inhibited by increasing levels of O2 and ceased above 50% O2. Vein endothelial cells could recover from up to 24 h of hyperoxic exposure when given fresh medium, but not after 48 h. Artery-derived cells were more sensitive to O2 than were vein-derived cells. Complete medium without endothelial cells, preincubated 24 h in 95% O2, lost its ability to support cell growth under normoxic conditions. Exposing individual medium components to high O2 demonstrated that purified natural ECGF and recombinant acidic or basic FGF were all inactivated by O2. Human recombinant superoxide dismutase prevented FGF inactivation. O2 inactivation of essential growth factors could thus have major consequences for lung development or repair of injured capillaries in infants or adults inspiring high levels of O2.