| Thrombin downregulates thrombomodulin expression and activity in primary human endothelial cells. | |
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MedLine Citation:
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PMID: 18568955 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Thrombomodulin (TM) is a cell surface anticoagulant glycoprotein that plays a key role in the protein C pathway. TM expression in endothelial cells may be modulated by a variety of extracellular signals. Most notably, TM has been shown to be downregulated by inflammatory mediators, such as tumor necrosis factor-alpha and lipopolysaccharide. The objective of this study was to determine the effect of thrombin on TM expression and activity. Thrombin resulted in reduced TM in primary cultures of human endothelial cells by approximately 40% at the level of mRNA, protein, and activity. These effects were blocked by the thrombin inhibitor hirudin. These results suggest that activation of the coagulation cascade may result in a positive-feedback loop consisting of thrombin-mediated repression of TM-dependent protein C activation. |
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Authors:
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Chantal Séguin; Md Ruhul Abid; Katherine C Spokes; William C Aird |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Endothelium : journal of endothelial cell research Volume: 15 ISSN: 1029-2373 ISO Abbreviation: Endothelium Publication Date: 2008 May-Jun |
Date Detail:
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Created Date: 2008-06-23 Completed Date: 2008-08-06 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9412590 Medline TA: Endothelium Country: United States |
Other Details:
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Languages: eng Pagination: 143-8 Citation Subset: IM |
Affiliation:
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Division of Molecular and Vascular Medicine and The Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA. seguin@muhc. mcgill.ca |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Cells, Cultured Endothelial Cells / drug effects*, physiology Endothelium, Vascular / cytology, drug effects*, physiology Gene Expression Regulation / drug effects* Hirudins / pharmacology Humans Protease Inhibitors / pharmacology RNA, Messenger / metabolism Thrombin / antagonists & inhibitors, pharmacology* Thrombomodulin / metabolism*, physiology Time Factors Umbilical Veins / cytology |
| Grant Support | |
ID/Acronym/Agency:
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HL60585-02/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Hirudins; 0/Protease Inhibitors; 0/RNA, Messenger; 0/Thrombomodulin; EC 3.4.21.5/Thrombin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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