ROLE OF GLYCOSAMINOGLYCANS IN VENOUS DISE ASE - MODE OF ACTION OF SOME FLAVONOID DRUGS

Varicous vein walls differ from normal veinous walls by an important l oss of their collagen content and an increase of their glycosaminoglyc an content, essentially of hyaluronan. The decrease in fibrous protein content can be attributed to increased proteolytic (collagenolytic) a ctivity as well as to free radicals. Glycosaminoglycan increase reflec ts a disregulation of the normal program of matrix biosynthesis by the cells of varicous vein wall, essentially smooth muscle cells. Some fl avonoid drugs are capable of correcting these deviations by decreasing proteolytic attack on fibrous proteins and the accumulation of proteo glycans and hyaluronan. These effects, due to interactions between fla vonoid drugs and the cells and fibrous proteins of the veinous wall di ffer according to the nature of such drugs. A hypothesis is proposed t o explain these differences in the intensity of action of flavonoid dr ugs with apparently closely related structures, based on the conformat ion of these drugs and their interaction with the triple helical struc ture of collagen fibers as well as with the cell membranes.