HDL AND APOLIPOPROTEIN-A-I PROTECT ERYTHROCYTES AGAINST THE GENERATION OF PROCOAGULANT ACTIVITY

The appearance of anionic lipids on the extracellular surface of cells is required for the formation of the procoagulant complex that leads to the activation of prothrombin. Procoagulant activity would be expec ted to be inhibited by substances that stabilize the membrane structur e and hence inhibit the transbilayer diffusion of phosphatidylserine f rom the cytoplasmic to the extracellular surface of the plasma membran e. The generation of procoagulant activity in human erythrocytes by A2 3187 and Ca2+ is inhibited by apolipoprotein A-I, its amphipathic pept ide analogues, and high-density lipoprotein (HDL). These agents do not inhibit the Ca2+ loading of erythrocytes by A23187, nor do they inhib it the activation of prothrombin once the cells have been incubated at 37 degrees C with A23187 and Ca2+. Transbilayer diffusion of fluoresc ently labeled phosphatidylserine is inhibited by apolipoprotein A-I. T hese findings indicate that class A amphipathic helixes as well as lip oprotein particles and liposomes inhibit the transbilayer diffusion of phospholipids and procoagulant activity. This activity may contribute to the protective role of HDL against arteriosclerosis and thrombosis .