Analysis of the connective tissue matrix and proteolytic activity of primary varicose veins

Abstract

Purpose: Valvular incompetence and venous wall abnormalities have been suggested as primary etiologic factors responsible for the development of varicose veins. This study was conducted to evaluate the connective tissue constituents of greater saphenous varicosities. Proteolytic activity, a factor that can lead to matrix degradation and cause weakening and dilation of the venous wall, was also assessed.Methods: The collagen and elastin contents of 16 nonthrombophlebitic greater saphenous varicose veins (VV) and seven normal greater saphenous veins (NV) were quantified. In addition, four duplex scanning-confirmed competent segments of greater saphenous veins (i.e., potential varicose veins [PV]) affected by varicosis at alternate sites were analyzed. Proteolytic activity was determined by zymography and radiolabeled substrate assay.Results: The content of collagen was significantly increased in the VV and PV compared with NV (VV = 189 ± 7 mg/gm, PV = 189 ± 9 mg/gm vs NV = 144 ± 10 mg/gm, p < 0.05). Conversely, the elastin content in the VV and PV was significantly reduced (VV = 53 ± 3 mg/gm, PV = 50 ± 4 mg/gm vs NV = 74 ± 4 mg/gm, p < 0.05). The collagen to elastin ratio demonstrated an alteration in VV and PV compared with NV (VV = 3.7 ± 0.3, PV = 3.9 ± 0.4 vs NV = 2.0 ± 0.2, p < 0.05). Casein and gelatin zymography did not demonstrate significant qualitative differences in the enzymatic activities among the three groups. Quantitative analysis of the elastase activity in the venous tissues was similarly not appreciably altered (VV = 5.1 ± 0.2 U/gm, PV = 5.3 ± 0.2 U/gm vs NV = 5.7 ± 0.3 U/gm).Conclusion: A significant increase in the collagen content and a significant reduction in the elastin content of VV were demonstrated. The net increase in the collagen/elastin ratio is indicative of an imbalance in the connective tissue matrix. The biochemical profile of PV was similar to VV and significantly different from NV. These preliminary data support the presence of connective tissue abnormalities before valvular insufficiency. In addition, the absence of an increase in the proteolytic activity excludes enzymatic matrix degradation as an essential component in the formation of venous varicosities.