Modulation of Endothelial Function by Hypoxia: Perturbation of Barrier and Anticoagulant Function, and Induction of a Novel Factor X Activator

摘要: Exposure of the vessel wall to hypoxemia is a central feature ischemic cardiovascular disease. This led us examine perturbation endothelial cell properties under hypoxia. An atmosphere pO2 12 mmHg not lethal cells for up five days, but barrier function was impaired. Increased passage macromolecule tracers were observed in time-and dose-dependent manner and electron microscopy demonstrated small gaps (0.5 — 1.0 µm) between cells. Expression anticoagulant cofactor thrombomodulin also perturbed: activity antigen decreased parallel. Northern blots showed almost complete suppression hypoxic culture. Furthermore, synthesis other proteins, such as fibronectin, slightly enhanced In addition these cofactor, displayed noval procoagulant distinct from tissue factor. Further study revealed that cultures directly activated Factor X, assessed by functional assays SDS-PAGE. this no activation IX or prothrombin observed. The hypoxia-induced X activator membrane-associated, required calcium form Xa, inhibited HgCl2 PMSF, had Km ≈ 25 µg/ml. Co-incubation with cycloheximide prevented expression activity, suggesting protein its expression. These perturbations reversible following reoxygenation. data indicate hypoxia imposes selective on function, possible contribution vascular dysfunction ischemia.