Document Detail


Role of the tissue factor pathway in synovial inflammation.
MedLine Citation:
PMID:  12632417     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Clinical and experimental evidence suggests that extravascular fibrin deposition in arthritic joints is prominent and deleterious. The aim of this study was to investigate the contributions of tissue factor (TF) and its inhibitor, TF pathway inhibitor (TFPI), in arthritis. METHODS: Synovial tissue specimens obtained from 10 patients with rheumatoid arthritis (RA) and 12 patients with osteoarthritis (OA) were scored histologically for inflammation and fibrin content. TF and TFPI levels were assayed at antigenic and functional levels. TF messenger RNA (mRNA) levels were determined using RNase protection assays. The effect of TF inhibition in murine antigen-induced arthritis (AIA) was assessed by administering systemically active site-blocked activated factor VIIa (FVIIai). RESULTS: Functional TF activity was significantly increased in synovial membranes from RA patients compared with those from OA patients. In contrast, no difference in TF mRNA and TF antigenic levels was observed between these 2 groups. This discrepancy can be accounted for by TFPI, because we observed a negative correlation between TF activity and TFPI activity. There was a significant difference between the RA and OA groups in terms of synovial inflammation, with more inflammation observed in the RA group. Most importantly, TF activity was associated with fibrin (P = 0.024) and with histologic inflammation (P = 0.03) scores. In AIA, inhibition of TF-induced coagulation by FVIIai led, on day 9 of arthritis, to decreased synovial thickness and decreased articular cartilage damage, although only the latter difference between controls and treated mice reached significance (P < 0.04). Finally, in FVIIai-treated mice, there was a strong negative association between the prothrombin time and intraarticular fibrin deposition. CONCLUSION: Our results show that TF expression in arthritic synovial tissue favors extravascular coagulation and may play a role in inflammation in RA. In this context, TF inhibitors may be of therapeutic value.
Authors:
Nathalie Busso; Carole Morard; Roberto Salvi; Veronique Péclat; Alexander So
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Arthritis and rheumatism     Volume:  48     ISSN:  0004-3591     ISO Abbreviation:  Arthritis Rheum.     Publication Date:  2003 Mar 
Date Detail:
Created Date:  2003-03-12     Completed Date:  2003-03-25     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0370605     Medline TA:  Arthritis Rheum     Country:  United States    
Other Details:
Languages:  eng     Pagination:  651-9     Citation Subset:  AIM; IM    
Affiliation:
Laboratoire de Rhumatologie, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. Nathalie.Busso@chuv.hospvd.ch
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MeSH Terms
Descriptor/Qualifier:
Aged
Animals
Arthritis, Experimental / prevention & control
Arthritis, Rheumatoid / metabolism*,  pathology
Dansyl Compounds / therapeutic use
Disease Models, Animal
Factor VIIa / therapeutic use
Female
Fibrin / metabolism
Fibrinolytic Agents / metabolism*,  pharmacology
Hindlimb / metabolism,  pathology,  radionuclide imaging
Humans
Immunohistochemistry
Lipoproteins / genetics,  metabolism*,  pharmacology
Male
Mice
Mice, Inbred C57BL
Middle Aged
Osteoarthritis / metabolism*,  pathology
RNA, Messenger / metabolism
Synovitis / metabolism*,  pathology
Thromboplastin / genetics,  metabolism*
Chemical
Reg. No./Substance:
0/Dansyl Compounds; 0/Fibrinolytic Agents; 0/Lipoproteins; 0/RNA, Messenger; 0/dansyl-glutamyl-glycyl-arginyl-factor VIIa; 0/lipoprotein-associated coagulation inhibitor; 9001-31-4/Fibrin; 9035-58-9/Thromboplastin; EC 3.4.21.21/Factor VIIa

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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