Premium
Increased TIMP/MMP ratio in varicose veins: a possible explanation for extracellular matrix accumulation
Author(s) -
BadierCommander Cécile,
Verbeuren Tony,
Lebard Christian,
Michel JeanBaptiste,
Jacob MariePaule
Publication year - 2000
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/1096-9896(2000)9999:9999<::aid-path670>3.0.co;2-1
Subject(s) - varicose veins , extracellular matrix , matrix metalloproteinase , plasminogen activator , extracellular , chemistry , zymography , anatomy , medicine , pathology , endocrinology , biochemistry , surgery
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. Copyright © 2000 John Wiley & Sons, Ltd.