Tissue inhibitor of metalloproteinase-1 is increased in the saphenofemoral junction of patients with varices in the leg.
OBJECTIVE
The goal of the present study was to examine the role of matrix metalloproteinase (MMP) activity in the development of varicose changes in the superficial veins of the lower extremity.


METHODS
Normal-caliber vein segments from the saphenofemoral junction were harvested from patients undergoing saphenous vein ligation for varices and from patients undergoing infrainguinal bypass graft procedures. The activity and quantity of MMPs and their inhibitors (tissue inhibitors of metalloproteinases [TIMPs]) in the vein segments were compared. Vein segments were obtained from 13 patients. Seven patients had varicose disease in the leg, including 6 women and 1 man (average age, 48 years). Six patients had no evidence of varicose disease, including 2 women and 4 men (average age, 59 years). Proteolytic activity was determined with substrate gel zymography, and enzyme content was determined with Western immunoblotting using monoclonal antibodies directed against MMP-2, MMP-3, MMP-9, TIMP-1, TIMP-2, and alpha2-macroglobulin. Signals were quantified by scanning densitometry and normalized to a positive control (densitometric index [DI]). Immunohistochemistry was performed for enzyme localization.


RESULTS
Zymography did not detect a difference between groups at loci consistent with the major MMPs; however, a small but significant decrease in proteolytic activity was noted in veins from patients with varices. TIMP-1 is increased in vein segments from patients with varices (DI 0.8 +/- 0.1 vs 0.2 +/- 0.05, P < .05) while MMP-2 levels were decreased (DI 1.5 +/- 0.3 vs 0.5 +/- 0.1, P < .05). Immunohistochemistry localized MMPs to the adventitia of the vein wall.


CONCLUSIONS
A decrease in proteolytic activity may be responsible for the histological and structural alterations leading to varicose degeneration of superficial lower extremity veins.
Parra
J R
JR
Division of Vascular Surgery, Medical College of Wisconsin, Milwaukee, USA.
Cambria
R A
RA
Hower
C D
CD
Dassow
M S
MS
Freischlag
J A
JA
Seabrook
G R
GR
Towne
J B
JB
D015153:Blotting, Western; D017364:Collagenases / Q000032:analysis; D005260:Female; D005268:Femoral Vein / Q000201:enzymology*; D018093:Gelatinases / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020781:Matrix Metalloproteinase 1; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D061965:Matrix Metalloproteinase Inhibitors; D008666:Metalloendopeptidases / Q000032:analysis; D012501:Saphenous Vein / Q000201:enzymology*; D019714:Tissue Inhibitor of Metalloproteinases / Q000032:analysis*; D014648:Varicose Veins / Q000201:enzymology*
D061965:Matrix Metalloproteinase Inhibitors; D019714:Tissue Inhibitor of Metalloproteinases; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1