REGULATION OF ENDOTHELIAL-CELL PROTEIN-C ACTIVATION BY NATIVE AND OXIDIZED LOW-DENSITY-LIPOPROTEIN

The effects of native LDL and Ox-LDL and HDL on endothelial cell protein C activation were examined. Ox-LDL, which is postulated to contribute to cardiovascular disease, markedly suppressed activation of protein C, an important vascular anticoagulant activity. This effect was seen with both human venous and arterial endothelial cells. Endothelial cells modified LDL to a form that reduced protein C activation, an effect prevented by the anti-oxidant, probucol. Endothelial cells are known to express the acetyl LDL (scavenger) receptor, which binds chemically modified and Ox-LDL. The effect of Ox-LDL on protein C activation does not appear to result from uptake via the acetyl LDL receptor, since a known scavenger receptor antagonist (fucoidin) did not inhibit the oxidized LDL effect. In contrast to the results with Ox-LDL, native LDL and both native and oxidized HDL increased protein C activation. These data indicate that native and modified lipoproteins regulate blood coagulation by affecting vascular anticoagulant activity and suggest mechanisms that may link modified lipoproteins with both vascular disease and thrombosis.