Jose R. Parra

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 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. CONCLUSION A decrease in proteolytic activity may be responsible for the histological and structural alterations leading to varicose degeneration of superficial lower extremity veins.

Takayasu’s disease

Takayasus arteritis (TA) is a chronic inflammatory disease of unknown etiology that can produce stenosis, occlusion, or aneurysmal degeneration of large arteries. TA occurs worldwide but disproportionately affects young females of Asian descent. A variable acute phase of largely constitutional symptoms is followed by a chronic phase in which symptoms related to arterial compromise predominate. Diagnosis is made using a combination of clinical and angiographic criteria. Initial therapy involves the use of corticosteroids to induce remission of acute phase activity, with the addition of cytotoxic medications for nonresponders. Angioplasty and stenting can be used in the treatment of shorter stenoses such as those encountered in the renal arteries. Surgical bypass is the preferred treatment of longer segment stenoses and occlusions. Bypass grafts should originate from unaffected arteries to ensure durable inflow. Endovascular therapy is effective initially but long-term durability data are lacking.

Tissue Inhibitor of Metalloproteinase is Increased in the Saphenofemoral Junction of Patients with Varicosities in the Leg

Purpose: 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 α 2 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. Conclusion: A decrease in proteolytic activity may be responsible for the histological and structural alterations leading to varicose degeneration of superficial lower extremity veins. (J Vasc Surg 1998;28:669-75.)