| Description |
The effects of native and oxidized low density lipoprotein (LDL) and high density lipoprotein (HDL) on endothelial cell protein C activation were examined. Oxidized 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 human arterial endothelial cells. Endothelial cells modified LDL to a form which 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 oxidized LDL. The effect of oxidized 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 oxidized LDL, both native LDL and HDL increased protein C activation. These data indicate that native and modified lipoproteins may regulate blood coagulation by affecting vascular anticoagulant activity, and suggest mechanisms that may link modified lipoproteins with both vascular disease and thrombosis. |
