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[Endothelial cells and coagulation abnormalities].

Abstract
Endothelial cells have two important anticoagulant systems, heparan sulfate-antithrombin system and thrombomodulin-protein C system. Under physiological conditions, these two systems inhibit activation of coagulation on endothelial cells. However, under inflammatory conditions, tumor necrosis factor(TNF)-alpha or other cytokines produced by monocytes reduce the anticoagulant properties of endothelial cell by downregulating expression of heparan sulfate and thrombomodulin on endothelial cells. Antithrombin stimulates prostacyclin generation from endothelial cells by interacting with heparan sulfate of endothelial cells and generated prostacyclin inhibits TNF-alpha production by monocytes. Activated protein C inhibits TNF-alpha production by monocyte dependent of its protease activity. Thus, antithrombin and activated protein C might inhibit the endothelial perturbation induced by cytokines. Antithrombin regulates TNF-alpha induced tissue factor expression on endothelial cells by an unknown mechanism. Thus, antithrombin and activated protein C might be useful agents for treating coagulation abnormalities associated with sepsis or other inflammation because these agents inhibit not only coagulation but also downregulation of anticoagulant activities of endothelial cells.
AuthorsM Uchiba, K Okajima
JournalRinsho byori. The Japanese journal of clinical pathology (Rinsho Byori) Vol. 48 Issue 4 Pg. 308-13 (Apr 2000) ISSN: 0047-1860 [Print] Japan
PMID10810875 (Publication Type: English Abstract, Journal Article, Review)
Chemical References
  • Antithrombins
  • Cytokines
  • Protein C
  • Thrombomodulin
  • Tumor Necrosis Factor-alpha
  • Heparitin Sulfate
Topics
  • Antithrombins (metabolism, physiology)
  • Blood Coagulation Disorders (etiology)
  • Cytokines (physiology)
  • Down-Regulation
  • Endothelium, Vascular (cytology, metabolism)
  • Heparitin Sulfate (metabolism, physiology)
  • Humans
  • Protein C (metabolism, physiology)
  • Thrombomodulin (metabolism, physiology)
  • Tumor Necrosis Factor-alpha (physiology)

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