EFFECT OF AESCINE ON HYPOXIA-INDUCED ACTIVATION OF HUMAN ENDOTHELIAL-CELLS

Phlebotonic drugs are very often old drugs which improve symptoms in c hronic venous insufficiency but their precise mechanism remains unclea r. One reason for this lack of information is our poor understanding o f the aetiology of the varicose vein. One hypothesis which is being mo re and more substantiated is that the origin of the disease lies in th e activation of the endothelium during blood stasis, leading to a casc ade of reactions which, in the long term, alter the structure of the v ein wall. In this work, we tested aescine (Reparil i.v. form), a phleb otonic drug, in an in vitro model which mimics this situation, i.e. hu man endothelial cells exposed to hypoxic conditions. Aescine was shown to inhibit 2 important steps of the activation of endothelial cells i ncubated 120 min under hypoxia: the decrease in ATP content, which is the starting point of the activation cascade, and the increase in the activity of phospholipase A(2), an enzyme responsible for the release of precursors of inflammatory mediators. Hypoxia-activated endothelial cells also increase their adhesiveness for neutrophils. This process could also be prevented in a dose-dependent manner if endothelial cell s were incubated in the presence of aescine. This inhibition was confi rmed by morphological observations in scanning electron microscopy. Al l 3 effects were already evidenced at 100 ng/ml and were maximal at 75 0 ng/ml. These effects obtained at very low concentrations probably re present one of the main molecular and cellular mechanisms that underli e, among others, protection of the vessel wall. Objective criteria for our understanding of the preventive action of this phlebotonic drug a re, thus, provided.