INTRINSIC PROCOAGULANT SURFACE-INDUCED BY HYPERCHOLESTEROLEMIA ON RABBIT AORTIC ENDOTHELIUM

The effect of hyperlipidaemia on endothelial cell haemostatic properti es was examined using ex vivo studies on aortic segments obtained from fat-fed Chinchilla rabbits, mounted in a template device which expose d the luminal surface. Exposure of arterial endothelium to lipids resu lted in marked enhancement of externally exposed anionic phospholipids , detected using either fluorescence microscopy with the probe merocya nine 540 or by binding of I-125-polymyxin B and I-125-Annexin V. Consi stent with the known procoagulant properties of anionic phospholipid, following the lipid and cholesterol-rich dict intake, intact endotheli al cells demonstrated enhanced binding of radioiodinated factors IX/IX a and Xa, and enhanced factor IXa/VIII-dependent factor X activation a nd factor Xa-factor Va-mediated prothrombin activation. Both factor Xa and thrombin formation were blocked, in large part, by polymyxin B, s uggesting dependence of the reaction on anionic phospholipids. Consist ent with these results, evidence of increased activation of the coagul ation mechanism in vivo was observed in hyperlipidaemic animals, as as sessed by a three-fold increase in levels of circulating antithrombin- protease complexes, compared with normolipidaemic controls.