[Cytochromes P450, vascular tone varicosis]

Chronic venous insufficiency is a complex pathology that is characterised by various symptoms such as venous hypertension, endothelium dysfunction, vascular wall remodelling due to smooth muscle cell hypertrophy and inflammation resulting from the release of pro-inflammatory cytokines from invading leucocytes. Age, hormonal excess, multiparity, sedentariness and prolonged heat exposure represent the main risk factors among many others including hypoxia and shear stress which also influence varicose pathology. Some members of the large cytochrome P450 (CYP) family that are involved in the biotransformation of steroids and arachidonic acid have been shown to be expressed in various cell types (endothelial cells, smooth muscle cells, macrophages) of cardiovascular tissues. The vascular metabolites produced by CYPs are important factors in the regulation of the vascular tone. Most CYPs are markedly expressed in all the cell types of varicose veins in relation to the overall vascular remodelling associated with smooth muscle hypertrophy and periendothelial leucocyte infiltration. Because CYPs produce various vasoactive arachidonic acid metabolites, their increased expression could play a role in the impairement of the vascular tone which is characteristic of varicose veins. Furthermore, polymorphisms, particularly the CYP3A5 polymorphism, may promote changes in the level of expression of CYPs and thus may influence varicose vein formation or functions. This suggests that CYP modulators could be potentially active drugs to treat chronic venous insufficiency symptoms and control its evolution.