PERFUSED HUMAN SAPHENOUS VEINS FOR THE STUDY OF THE ORIGIN OF VARICOSE-VEINS - ROLE OF THE ENDOTHELIUM AND OF HYPOXIA

If venous stasis due to blood stagnation has been recognized to be inv olved in the development of varicose veins, the mechanism linking this situation to the modifications of the venous wall observed in varicos es is still unclear. In order to study this mechanism, human saphenous veins were incubated in normoxic or hypoxic conditions and the intera ctions between the endothelium and neutrophils were investigated. We o bserved that many neutrophils adhered to the endothelium of veins incu bated in hypoxic conditions rather than in normoxia and that these adh erent neutrophils were activated: they released high amounts of supero xide anion and of leukotriene B-4. Studies in scanning electron micros copy confirmed the increased neutrophil adherence to the endothelium a s well as their activation. These results were then related to the his tological observation of varicose veins. These veins show a thickening of the media with extracellular matrix deposit as well as an alterati on of the elastic lamina with the presence of smooth muscle cells in t he intima. These results are in agreement with in vitro studies on iso lated endothelial cells. They all show that hypoxia is able to activat e endothelial cells: they release inflammatory mediators and become ad hesive for neutrophils which are then activated. These activated leuko cytes release free radicals and proteases which are able to degrade th e extracellular matrix. In addition, hypoxia-activated endothelial cel ls secrete growth factors which will trigger smooth muscle cell prolif eration and the synthesis of extracellular matrix components. Altogeth er and because they are frequently repeated, these processes could eve ntually lead to alterations of the venous wall similar to those observ ed in varicose veins.