Inhibitory effect of TIMP influences the morphology of varicose veins.
OBJECTIVE
Imbalance of matrix metalloproteinase enzymes (MMP) and their inhibitors (TIMPs) may contribute to the development of varicose veins. We hypothesised that, histological changes in varicose vein wall correlate with alterations in expression of MMP/TIMP.


METHODS
Varicose veins (n=26) were compared with great saphenous vein (GSV) segments (n=11) from arterial bypass, and with arm and neck veins from fistula and carotid operations (n=13). Varicose vein wall thickness was measured, enabling categorisation as atrophic and hypertrophic. MMP-2, MT1-MMP, TIMP-2, and TIMP-3 expression were quantitatively analysed by immunohistochemistry.


RESULTS
There was significantly higher expression of TIMP-2 (immunopositive area 4.34% versus 0.26%), linked with connective tissue accumulation in the tunica media of varicose veins as compared with arm and neck vein controls. TIMP-2 and TIMP-3 expression was higher in hypertrophic than atrophic segments (3.2% versus 0.99% for TIMP-2, 1.7% versus 0.08% for TIMP-3). Similarly, TIMP-2 and TIMP-3 had elevated expression in the thicker proximal varicose vein segments compared to distal (4.3% versus 1.3% for TIMP-2 and 0.94% versus 0.41% for TIMP-3).


CONCLUSIONS
This study linked morphological changes in varicose vein walls with MMP/TIMP balance. A higher TIMP expression favours deposition of connective tissue and thus thicker vein wall, reducing matrix turnover by suppression of protease activity.
Aravind
B
B
Department of Surgery and Cancer, Faculty of Medicine, Imperial College, and Department of Histopathology, Charing Cross Hospital, London, UK.
Saunders
B
B
Navin
T
T
Sandison
A
A
Monaco
C
C
Paleolog
E M
EM
Davies
A H
AH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001284:Atrophy; D016022:Case-Control Studies; D003238:Connective Tissue / Q000737:chemistry / Q000473:pathology; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D006984:Hypertrophy; D007150:Immunohistochemistry; D008131:London; D008297:Male; D053511:Matrix Metalloproteinase 14 / Q000032:analysis; D020778:Matrix Metalloproteinase 2 / Q000032:analysis; D008875:Middle Aged; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000032:analysis*; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000032:analysis*; D017540:Tunica Media / Q000737:chemistry / Q000473:pathology; D014648:Varicose Veins / Q000378:metabolism* / Q000473:pathology; D014680:Veins / Q000737:chemistry* / Q000473:pathology; D055815:Young Adult
C088390:TIMP3 protein, human; D019717:Tissue Inhibitor of Metalloproteinase-3; D019716:Tissue Inhibitor of Metalloproteinase-2; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14