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Papers In Press, published online ahead of print October 27, 2000
Cardiovascular Biology, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104
Corresponding Author: Naomi-Esmon{at}omrf.ouhsc.edu
Although lipid oxidation products are usually associated with tissue injury, it is now recognized that they can also contribute to cell activation and elicit anti-inflammatory lipid mediators. In this study, we report that membrane phospholipid oxidation can modulate the hemostatic balance. Oxidation of natural phospholipids results in an increased ability of the membrane surface to support the function of the natural anticoagulant, activated protein C (APC), without significantly altering the ability to support thrombin generation. Lipid oxidation also potentiated the ability of protein S to enhance APC mediated factor Va inactivation. Phosphatidylethanolamine, phosphatidylserine and polyunsaturation of the fatty acids were all required for the oxidation dependent enhancement of APC function. A subgroup of thrombotic patients with anti-phospholipid antibodies specifically blocked the oxidation dependent enhancement of APC function. Since leukocytes are recruited and activated at the thrombus or sites of vessel injury, our findings suggest that after the initial thrombus formation, lipid oxidation can remodel the membrane surface resulting in increased anticoagulant function, thereby reducing the thrombogenicity of the thrombus or injured vessel surface. Anti-phospholipid antibodies that block this process would therefore be expected to contribute to thrombus growth and disease.
J. Biol. Chem, 10.1074/jbc.M005931200
Submitted on July 6, 2000
Revised on October 27, 2000
Accepted on October 26, 2000
Lipid oxidation enhances the function of activated protein C
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