Hypoxia modulates the barrier and coagulant function of cultured bovine endothelium. Increased monolayer permeability and induction of procoagulant properties.
Open Access
- 1 April 1990
- journal article
- research article
- Published by American Society for Clinical Investigation in Journal of Clinical Investigation
- Vol. 85 (4) , 1090-1098
- https://doi.org/10.1172/jci114540
Abstract
Exposure of cultured endothelium to environments with low concentrations of oxygen, in the range of those observed in pathophysiologic hypoxemic states in vivo, compromises cellular barrier and coagulant function. An atmosphere with PO2 approximately 14 mm Hg was not lethally toxic to endothelial cultures, but cells became larger and exhibited small intercellular gaps. At low oxygen concentrations, passage of macromolecular tracers through hypoxic endothelial monolayers was accelerated in a time- and dose-dependent manner, presumably by a paracellular pathway via the gaps. Cell surface coagulant properties of the endothelium were also perturbed. At PO2 approximately 14 mm Hg thrombomodulin antigen and functional activity on the cell surface were diminished by 80-90%, and Northern blots demonstrated suppression of thrombomodulin mRNA. The decrease in thrombomodulin was twice as great compared with the general decline in total protein synthesis in hypoxia. In addition, expression of a direct Factor X activator developed under hypoxic conditions; the activator was membrane-associated and expressed on the surface of intact cultures, Ca-dependent, inhibited by HgCl2 but not PMSF, and had Km approximately 25 micrograms/ml for the substrate at pH 7.4. Synthesis of the activator was blocked by inclusion of cycloheximide, but not warfarin, in the culture medium. These results demonstrate that endothelial function is perturbed in a selective manner in the presence of low concentrations of oxygen, providing insights into mechanisms which may contribute to vascular dysfunction in hypoxemic states.This publication has 55 references indexed in Scilit:
- Long-chain acylcarnitines mediate the hypoxia-induced increase in alpha 1-adrenergic receptors on adult canine myocytes.Circulation Research, 1987
- Human thrombomodulin: complete cDNA sequence and chromosome localization of the geneBiochemistry, 1987
- Transendothelial transfer of macromolecules in vitro.1987
- Endothelial monolayer permeability to macromolecules.1987
- Glycolytic activity and enhancement of serotonin uptake by endothelial cells exposed to hypoxia/anoxia.Circulation Research, 1987
- The Regulation of Natural Anticoagulant PathwaysScience, 1987
- REDUCED OXYGEN-TENSION INDUCES PULMONARY ENDOTHELIUM TO RELEASE A PULMONARY SMOOTH-MUSCLE CELL MITOGEN(S)Published by Elsevier ,1987
- Histamine type I receptor occupancy increases endothelial cytosolic calcium, reduces F-actin, and promotes albumin diffusion across cultured endothelial monolayers.The Journal of cell biology, 1986
- Induction characteristics of oxygen regulated proteinsInternational Journal of Radiation Oncology*Biology*Physics, 1986
- STUDIES ON INFLAMMATIONThe Journal of cell biology, 1961