TISSUE INHIBITOR OF METALLOPROTEINASE-1 IS INCREASED IN THE SAPHENOFEMORAL JUNCTION OF PATIENTS WITH VARICES IN THE LEG

Purpose: The goal of the present study was to examine the role of matr ix metalloproteinase (MMP) activity in the development of varicose cha nges 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 activit y and quantity of MMPs and their inhibitors (tissue inhibitors of meta lloproteinases [TIMPs]) in the vein segments mere compared. Vein segme nts were obtained from 13 patients. Seven patients had varicose diseas e 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 West ern immunoblotting using monoclonal antibodies directed against MMP-2, MMP-3, MMP-9, TIMP-1, TIMP-2, and alpha(2)-macroglobulin. Signals wer e quantified by scanning densitometry and normalized to a positive con trol (densitometric index [DI]). Immunohistochemistry was performed fo r enzyme localization. Results: Zymography did not detect a difference between groups at loci consistent with the major MMPs; however, a sma ll 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). Im munohistochemistry localized MMPs to the adventitia of the vein wall. Conclusion: A decrease in proteolytic activity may be responsible for the histological and structural alterations leading to varicose degene ration of superficial lower extremity veins.