[Extracellular matrix and vascular pathologies. Role of proteases and oxygenated free radicals]

Vessel walls contain several types of mesenchymatous cells and many representatives of the 4 groups of macromolecules of the extracellular matrix secreted by those cells. Under normal conditions, a proportion of the macromolecules of the vascular wall is broken down by the neosynthesis of an equivalent amount of the same macromolecules which are then integrated into functional structures. Under pathological conditions, an excessive amount of macromolecules is broken down by proteases and free radicals, without any compensatory increase in biosynthesis and without the integration of biosynthesised compounds into functional structures. Thus, for example, a varicose saphenous vein may lose as much as 60 per cent of the collagen of its wall. Attempts at symptomatic treatment designed to combat this loss of substance, a notable cause of weakening of he vessel wall, are based upon three principles: inhibition of catabolic enzymes, chiefly proteases (e.g. leucocyte elastase), responsible for excessive breakdown; uptake of oxygenated free radicals; "substrate protection" designed to preserve undamaged fibrous proteins and to help the integration of neosynthesized compounds into functional structures. Only medications which act as "substrate protectors" are capable of coping at one and the same time with the effects of proteases and those of oxygenated free radicals.