Document Detail


Increased TIMP/MMP ratio in varicose veins: a possible explanation for extracellular matrix accumulation.
MedLine Citation:
PMID:  10951407     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Primary varicose veins are functionally characterized by venous back-flow and blood stagnation in the upright position. Dilatation and tortuosity provide evidence for progressive venous wall remodelling, with disturbance of smooth muscle cell/extracellular matrix organization. Affected areas are not uniformly distributed, some areas being hypertrophic, whereas others are atrophic or unaffected. In 12 varicose veins and ten control veins, the proteolytic enzyme/inhibitor balance which may participate in the remodelling of the venous wall was investigated. For this purpose, the presence and enzymatic activity of matrix metalloproteinases (MMP-2, MMP-9), tissue inhibitors of MMPs (TIMP-1, TIMP-2), urokinase-type (uPA) and tissue-type (tPA) plasminogen activators (PAs), and plasminogen activator inhibitor-1 (PAI-1) were quantified by western blot and gelatin or plasminogen-casein zymography. In addition, MMP-2, TIMP-1, TIMP-2, and PAI-1 levels were measured by ELISA. A high TIMP-1 level and a low MMP-2 level/activity were found in varicose veins (p<0.005), resulting in a three-fold increase in the TIMP-1/MMP-2 ratio in varicose versus control veins. Levels of PAs (uPA and tPA) as well as PAI-1 were both lower in varicose veins (p<0.005), with minimal change in the PAI/PA ratio. These results demonstrate that varicose veins are characterized by a higher than normal TIMP/MMP ratio, which may facilitate extracellular matrix accumulation in the diseased venous wall.
Authors:
C Badier-Commander; T Verbeuren; C Lebard; J B Michel; M P Jacob
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of pathology     Volume:  192     ISSN:  0022-3417     ISO Abbreviation:  J. Pathol.     Publication Date:  2000 Sep 
Date Detail:
Created Date:  2000-10-24     Completed Date:  2000-10-24     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0204634     Medline TA:  J Pathol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  105-12     Citation Subset:  IM    
Copyright Information:
Copyright 2000 John Wiley & Sons, Ltd.
Affiliation:
U460 INSERM, UFR de Médecine X. Bichat, 16 Rue H. Huchard, 75870 Paris Cedex 18, France. badier@bichat.inserm.fr
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MeSH Terms
Descriptor/Qualifier:
Adult
Blotting, Western
Extracellular Matrix / enzymology,  metabolism*
Female
Humans
Male
Matrix Metalloproteinase 2 / metabolism
Matrix Metalloproteinase 9 / metabolism
Matrix Metalloproteinases / metabolism*
Middle Aged
Plasminogen Activators / metabolism
Plasminogen Inactivators / metabolism
Tissue Inhibitor of Metalloproteinase-1 / metabolism
Tissue Inhibitor of Metalloproteinase-2 / metabolism
Tissue Inhibitor of Metalloproteinases / metabolism*
Varicose Veins / enzymology,  metabolism*
Chemical
Reg. No./Substance:
0/Plasminogen Inactivators; 0/Tissue Inhibitor of Metalloproteinase-1; 0/Tissue Inhibitor of Metalloproteinases; 127497-59-0/Tissue Inhibitor of Metalloproteinase-2; EC 3.4.21.-/Plasminogen Activators; EC 3.4.24.-/Matrix Metalloproteinases; EC 3.4.24.24/Matrix Metalloproteinase 2; EC 3.4.24.35/Matrix Metalloproteinase 9

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


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