Hypoxia Inhibits Tissue-Type Plasminogen Activator Production in Cultured Human Endothelial Cells: Role of Oxygen Radicals

In vitro experiments were designed to investigate the effect of low oxygen tensions on tissue-type plasminogen activator (t-PA) production by vascular endothelium. Cultured human umbilical vein endothelial cells were submitted for 1–8 h to hypoxia (30 mm Hg). t-PA antigen, measured by specific enzyme-linked immunosorbent assay (ELISA), was found significantly decreased either in culture supernatants or in cell lysates/extracellular matrix. By contrast, the secretion of plasminogen activator inhibitor-1 (PAI-1), also measured by specific ELISA, was not affected. Addition of superoxide dismutase (a superoxide anion scavenger) or oxypurinol (a xanthine oxidase inhibitor) to monolayers before hypoxia prevented t-PA modification. The flavonoid rutin (a hydroxyl radical scavenger) also presented a protective effect whereas catalase (a hydrogen peroxide scavenger) was inefficient. These results suggest that hypoxia stimulates endothelial cells to produce oxygen radicals and in particular xanthine oxidase-derived...