Lipid oxidation enhances the function of activated protein C

Although lipid oxidation products are usually associated with tissue injury , it is now recognized that they can also contribute to cell activation and elicit antiinflammatory lipid mediators. In this study, we report that mem brane phospholipid oxidation can modulate the hemostatic balance. Oxidation of natural phospholipids results in an increased ability of the membrane s urface to support the function of the natural anticoagulant, activated prot ein C (APC), without significantly altering the ability to support thrombin generation. Lipid oxidation also potentiated the ability of protein S to e nhance APC-mediated factor Va inactivation. Phosphatidylethanolamine, phosp hatidylserine, and polyunsaturation of the fatty acids were all required fo r the oxidation-dependent enhancement of APC function. A subgroup of thromb otic patients with anti-phospholipid antibodies specifically blocked the ox idation-dependent enhancement of APC function. Since leukocytes are recruit ed and activated at the thrombus or sites of vessel injury, our findings su ggest that after the initial thrombus formation, lipid oxidation can remode l the membrane surface resulting in increased anticoagulant function, there by reducing the thrombogenicity of the thrombus or injured vessel surface. Anti-phospholipid antibodies that block this process would therefore be exp ected to contribute to thrombus growth and disease.