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 involved in the development of varicose veins, the mechanism linking this situation to the modifications of the venous wall observed in varicoses is still unclear. In order to study this mechanism, human saphenous veins were incubated in normoxic or hypoxic conditions and the interactions between the endothelium and neutrophils were investigated. We observed that many neutrophils adhered to the endothelium of veins incubated in hypoxic conditions rather than in normoxia and that these adherent neutrophils were activated: they released high amounts of superoxide anion and of leukotriene B4. Studies in scanning electron microscopy confirmed the increased neutrophil adherence to the endothelium as well as their activation. These results were then related to the histological observation of varicose veins. These veins show a thickening of the media with extracellular matrix deposit as well as an alteration of the elastic lamina with the presence of smooth muscle cells in the intima. These results are in agreement with in vitro studies on isolated endothelial cells. They all show that hypoxia is able to activate endothelial cells: they release inflammatory mediators and become adhesive for neutrophils which are then activated. These activated leukocytes release free radicals and proteases which are able to degrade the extracellular matrix. In addition, hypoxia-activated endothelial cells secrete growth factors which will trigger smooth muscle cell proliferation and the synthesis of extracellular matrix components. Altogether and because they are frequently repeated, these processes could eventually lead to alterations of the venous wall similar to those observed in varicose veins.
Michiels
C
C
Laboratoire de Biochimie Cellulaire, Facultés Universitaires, Notre Dame de la Paix, Namur, Belgium.
Arnould
T
T
Thibaut-Vercruyssen
R
R
Bouaziz
N
N
Janssens
D
D
Remacle
J
J
D002448:Cell Adhesion; D015687:Cell Hypoxia / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D007975:Leukotriene B4 / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D009131:Muscle, Smooth, Vascular / Q000648:ultrastructure; D018375:Neutrophil Activation; D009504:Neutrophils / Q000502:physiology; D010477:Perfusion; D012501:Saphenous Vein / Q000378:metabolism / Q000648:ultrastructure; D013481:Superoxides / Q000378:metabolism; D014648:Varicose Veins / Q000209:etiology* / Q000473:pathology
D013481:Superoxides; D007975:Leukotriene B4