An endothelial cell-dependent pathway of coagulation

David Stern, P. Nawroth, D. Handley, W. Kisiel

Research output: Contribution to journalArticle

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Abstract

Although the endothelial cell is considered antithrombogenic, endothelium has recently been shown to participate in procoagulant reactions. In this report cultured bovine aortic endothelial cells are shown to propagate a procoagulant pathway starting with factor XI(a), leading to activation of factors IX, VIII, X, and prothrombin, culminating in fibrinopeptide A cleavage from fibrinogen and formation of a fibrin clot. Electron microscopic studies demonstrated that fibrin strands are closely associated with the endothelial cells. Endotoxin-treated endothelial cells, having acquired tissue factor activity, generated fibrinopeptide A in the presence of factors VII(a), IX, VIII, X, prothrombin, and fibrinogen. Factor X activation by factor VII(a) and tissue factor expressed by endothelial cells is 10 times greater in the presence of factors IX and VIII than in their absence. This indicates that on the perturbed endothelial cell surface, factors IX and VIII do not have an important role in the activation of factor X. Addition of platelets (108 per ml) augmented thrombin formation seen in the presence of endothelium alone by about 15-fold. Anti-human factor V IgG decreased this enhanced thrombin formation in the presence of platelets, indicating that factor V from platelets was playing an important role in thrombin formation. These data lead us to propose that endothelial cells can actively participate in procoagulant reactions. Although platelets can augment thrombin formation by these endothelial cell-dependent reactions, endothelial cells alone can lead to formation of a cell-associated fibrin clot. The endotoxin-treated endothelial cell provides a model of the thrombotic state supplying tissue factor to initiate coagulation and propagating the reactions leading to fibrin formation. This endothelial cell-dependent pathway suggests a central role for factors VIII and IX consistent with their importance in hemostatis.

Original languageEnglish (US)
Pages (from-to)2523-2527
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume82
Issue number8
DOIs
StatePublished - Jan 1 1985

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Endothelial Cells
Factor IX
Factor VIII
Fibrin
Thrombin
Thromboplastin
Fibrinopeptide A
Factor X
Factor VII
Blood Platelets
Prothrombin
Endotoxins
Fibrinogen
Endothelium
Factor XI
Factor V
Immunoglobulin G
Electrons

All Science Journal Classification (ASJC) codes

  • General

Cite this

An endothelial cell-dependent pathway of coagulation. / Stern, David; Nawroth, P.; Handley, D.; Kisiel, W.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 82, No. 8, 01.01.1985, p. 2523-2527.

Research output: Contribution to journalArticle

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