I have posted below what became a landmark paper that I had the privilege of co-authoring in the laboratory of an old friend and mentor, Dave Tilson who was the Chief of Surgery at St. Lukes/Roosevelt Hospital and a Chaired Professor at Columbia University. To summarize the findings of this study, we evaluated the amount of collagen and elastic tissue along with the enzymes that break down those proteins in the wall of abnormal varicose veins, normal veins in patients with varicose veins and normal veins that were left over from heart bypass patients. We identified abnormalities of the amount of collagen with increased amounts in both the varicose veins and the seemingly normal veins in varicose vein patients as compared with the normal veins of heart bypass patients. This paper identified the presence of connective tissue abnormalities before valvular insufficiency developed.
Analysis of the connective tissue matrix and proteolytic activity of primary varicose veins.
J Vasc Surg. 1993; 18(5):814-20 (ISSN: 0741-5214)
Gandhi RH; Irizarry E; Nackman GB; Halpern VJ; Mulcare RJ; Tilson MD
Department of Surgery, St. Luke's-Roosevelt Hospital Center, Columbia University, New York, NY.
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.