The interaction of β2-glycoprotein I with lysophosphatidic acid in platelet aggregation and blood clotting

beta(2)-Glycoprotein I (beta(2)-GPI) is a plasma protein that binds to oxidized low-density lipoprotein (LDL) and negatively charged substances, and inhibits platelet activation and blood coagulation. In this study, we investigated the interaction of beta(2)-GPI with a negatively charged lysophosphatidic acid (LPA) in platelet aggregation and blood clotting. Two negatively charged lysophospholipids, LPA and lysophosphatidylserine, specifically inhibited the binding of beta(2)-GPI to oxidized LDL in a concentration-dependent manner. Intrinsic tryptophan fluorescence studies demonstrated that emission intensity of beta(2)-GPI decreases in an LPA-concentration-dependent manner without a shift in wavelength maxima. LPA specifically induced the aggregation of beta(2)-GPI in phosphate-buffered saline, and in incubated plasma and serum, both of which are known to accumulate LPA by the action of lecithin-cholesterol acyltransferase and lysophospholipase D/autotaxin. beta(2)-GPI aggregated by LPA did not inhibit activated von Willebrand factor-induced aggregation, and did not prolong the activated partial thromboplastin time in blood plasma, in contrast to non-aggregated beta(2)-GPI. These results suggest that . beta(2)-GPI aggregated by the binding to LPA fails to inhibit platelet aggregation and blood clotting in contrast to nonaggregated beta(2)-GPI.