Metalloproteinase expression in venous aneurysms

Introduction: Although recognized with increasing frequency, the pathogenesis of venous aneurysms (VA) remains poorly understood. We evaluated 8 patients with 10 VA for the presence, localization and activity of metalloproteinases (MMPs). Methods: Tissue specimens from VA (n=8), normal saphenous vein (NSV n=7) and varicose veins (VV n=7 were compared by histology and immunohistochemistry (IHC). Histologic sections were stained with H&E, Movats pentachrome and toluidine blue, and IHC specimens with antibodies to CD68, MMP2, MMP9, and MMP13. Protein expression and enzyme activity were determined by Western immunoblotting and zymography. Results: Three of 4 patients with popliteal VA presented with edema and leg pain and the remaining patient with deep venous thrombosis (DVT) and pulmonary embolism (PE). The 5 popliteal VA were treated by; excision and reanastomosis (n=2) lateral venorrhaphy (n=2) and spiral saphenous vein graft (n=1). The 3 patients with 4 upper extremity VA had discomfort over a compressible mass. Two of the VA were excised and the remaining patients aneurysm ruptured spontaneously. The mesenteric VA, an incidental finding at laparotomy was excised. Thrombus was present in 2 popliteal, 1 upper extremity and in the mesenteric aneurysm. Histologically, VA and VV were characterized by fragmentation of the elastic lamellae, loss of smooth muscle cells (SMCs) and attenuation of the venous wall when compared to NSV. Varicose veins and VA also demonstrated increased expression of MMP-2, MMP-9 and MMP-13 in endothelial cells (ECs), SMCs and adventitial microvessels compared to NSV. Both pro-MMP-2 and pro-MMP-9 were detected by zymography in VA,VV and NSV but only MMP-2 activity was demonstrable. Conclusions: The structural changes in the venous wall in addition to the increased expression of MMP-2, MMP-9 and MMP-13 in VA compared to NSV and VV suggests a possible causal role for these MMPs in their pathogenesis.