Document Detail

Thrombin downregulates thrombomodulin expression and activity in primary human endothelial cells.
MedLine Citation:
PMID:  18568955     Owner:  NLM     Status:  MEDLINE    
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.
Chantal Séguin; Md Ruhul Abid; Katherine C Spokes; William C Aird
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Endothelium : journal of endothelial cell research     Volume:  15     ISSN:  1029-2373     ISO Abbreviation:  Endothelium     Publication Date:    2008 May-Jun
Date Detail:
Created Date:  2008-06-23     Completed Date:  2008-08-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9412590     Medline TA:  Endothelium     Country:  United States    
Other Details:
Languages:  eng     Pagination:  143-8     Citation Subset:  IM    
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.
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MeSH Terms
Cells, Cultured
Endothelial Cells / drug effects*,  physiology
Endothelium, Vascular / cytology,  drug effects*,  physiology
Gene Expression Regulation / drug effects*
Hirudins / pharmacology
Protease Inhibitors / pharmacology
RNA, Messenger / metabolism
Thrombin / antagonists & inhibitors,  pharmacology*
Thrombomodulin / metabolism*,  physiology
Time Factors
Umbilical Veins / cytology
Grant Support
Reg. No./Substance:
0/Hirudins; 0/Protease Inhibitors; 0/RNA, Messenger; 0/Thrombomodulin; EC

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