The effect of hypoxia on capillary endothelial cell function: modulation of barrier and coagulant function

Satoshi Ogawa, Revati Shreeniwas, Jerold Brett, Matthias Clauss, Martha Furie, David M. Stern

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Summary. As the cells forming the luminal vascular surface, endothelium is exposed to alterations in the vascular microenvironment, such as hypoxaemia. In this report we demonstrate that hypoxia, with pO2 as low as 12–14 mmHg, was not toxic to endothelium, but reversibly modulated central cellular functions essential for maintenance of homeostasis: permeability of monolayers to solutes increased in a dosedependent manner, and cell surface coagulant properties were shifted to promote activation of coagulation. The anticoagulant cofactor thrombomodulin was suppressed and an apparently novel activator of factor X, distinct from the classical extrinsic and intrinsic systems, was induced. The hypoxia‐induced factor X activator was cell surface‐associated, had properties of a cysteine protease, had Mr corresponding to ∼ 100 kDa. based on sodium dodecyl sulphatepolyacrylamide electrophoresis (SDS‐PAGE), and isoelectric point (pI) ∼ 5.0. These findings indicate that hypoxia dynamically modulates endothelial function providing insights into the contribution of microvascular endothelial dysfunction in the pathogenesis of vascular lesions.

Original languageEnglish (US)
Pages (from-to)517-524
Number of pages8
JournalBritish journal of haematology
Volume75
Issue number4
DOIs
StatePublished - Aug 1990

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Coagulants
cancer procoagulant
Endothelial Cells
Blood Vessels
Thrombomodulin
Cysteine Proteases
Surface Properties
Poisons
Vascular Endothelium
Isoelectric Point
Sodium Dodecyl Sulfate
Anticoagulants
Endothelium
Electrophoresis
Polyacrylamide Gel Electrophoresis
Permeability
Homeostasis
Maintenance
Hypoxia

ASJC Scopus subject areas

  • Hematology

Cite this

The effect of hypoxia on capillary endothelial cell function : modulation of barrier and coagulant function. / Ogawa, Satoshi; Shreeniwas, Revati; Brett, Jerold; Clauss, Matthias; Furie, Martha; Stern, David M.

In: British journal of haematology, Vol. 75, No. 4, 08.1990, p. 517-524.

Research output: Contribution to journalArticle

Ogawa, Satoshi ; Shreeniwas, Revati ; Brett, Jerold ; Clauss, Matthias ; Furie, Martha ; Stern, David M. / The effect of hypoxia on capillary endothelial cell function : modulation of barrier and coagulant function. In: British journal of haematology. 1990 ; Vol. 75, No. 4. pp. 517-524.
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AU - Stern, David M.

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AB - Summary. As the cells forming the luminal vascular surface, endothelium is exposed to alterations in the vascular microenvironment, such as hypoxaemia. In this report we demonstrate that hypoxia, with pO2 as low as 12–14 mmHg, was not toxic to endothelium, but reversibly modulated central cellular functions essential for maintenance of homeostasis: permeability of monolayers to solutes increased in a dosedependent manner, and cell surface coagulant properties were shifted to promote activation of coagulation. The anticoagulant cofactor thrombomodulin was suppressed and an apparently novel activator of factor X, distinct from the classical extrinsic and intrinsic systems, was induced. The hypoxia‐induced factor X activator was cell surface‐associated, had properties of a cysteine protease, had Mr corresponding to ∼ 100 kDa. based on sodium dodecyl sulphatepolyacrylamide electrophoresis (SDS‐PAGE), and isoelectric point (pI) ∼ 5.0. These findings indicate that hypoxia dynamically modulates endothelial function providing insights into the contribution of microvascular endothelial dysfunction in the pathogenesis of vascular lesions.

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