RELATIONSHIP BETWEEN VESSEL WALL 13-HODE PRODUCTION AND SUBENDOTHELIAL BASEMENT MEMBRANE THROMBORESISTANCE: INFLUENCE OF SALICYLATE

Abstract

In previous studies, we have reported that i) the basement membrane (BM) underlying endothelial cells was initially throm-boresistant; ii) 13-hydroxyoctadecadienoic acid (13-HODE) synthesized by endothelial cells from linoleic acid via the lipoxygenase pathway, contributed to the thromboresistance of the endothelium; and iii) salicylate (SAL) increased injured vessel wall thrombogenecity. Therefore, we performed studies to determine the relationship between injured vessel wall thrombogenecity, vessel wall 13-HODE and cAMP levels, and salicylate treatment. Injured vessel wall thrombogenecity was measured as the number of H-adenine platelet (3H-PLT) adherent to the subendothelial BM exposed by air injury in carotid arteries of rabbits treated with 0 or 100 mg/kg of SAL bid, given orally2. Vessel wall 13-HODE was measured as the amount of 13-HODE/cm produced by the vessel wall following stimulation with 10μ/M linoleic acid, and measured by HPLC. Vessel wall cAMP levels were measured by RIA. Four hours after air injury, there was 25.4 ± 2 3 2H-PLT/cm2 of exposed BM. This was associated with 15.9 ng/cm2 of 13-HODE and 308 pM/cm2 of cAMP (Table 1). In contrast, in rabbits treated with SAL, there was a 2-fold increase in platelet adhesion onto the injured carotid arteries. The increase in platelet adhesion was associated with a 65% decrease in 13-HODE production by the vessel wall and a modest (20%) decrease in cAMP level.We conclude that the lipoxygenase derived linoleic acid metabolite, 13-HODE contributes not only to the thromboresis-tance of the endothelium, but also to its underlying basement membrane.