Oxidized low density lipoprotein inhibits platelet plasma membrane Ca(2+)-ATPase

Oxidized low density lipoprotein (LDL) has been shown to enhance platelet activation. Since platelet activation is accompanied by an increase in cytosolic calcium, the effects of oxidized LDL on plasma membrane Ca(2+)-ATPase, plasma membrane fluidity and cytoplasmic calcium were studied in human platelets and purified platelet plasma membranes. Our results demonstrate that oxidized LDL, but not native LDL, inhibits the activity of Ca(2+)-ATPase in purified platelet plasma membranes (P < 0.01). Addition of the free radical scavenger alpha-tocopherol had no effect on the ability of oxidized LDL to inhibit the Ca(2+)-ATPase. An increased cytoplasmic calcium level in whole platelets was induced by oxidized LDL (P < 0.01), indicating that the plasma membrane Ca(2+)-extrusion pump may also be inhibited in vivo by oxidized LDL, although other mechanisms for the increase in cytoplasmic calcium are possible. Since no change in membrane fluidity was observed in platelet plasma membranes exposed to oxidized or native LDL as estimated by steady state trimethylammonium diphenylhexatriene (TMA-DPH) anisotropy, oxidized LDL does not affect the Ca(2+)-ATPase by grossly changing the membrane environment. The present results suggest that exposure of platelets to oxidized LDL causes inhibition of the plasma membrane Ca(2+)-ATPase which contributes to the observed increase in cytoplasmic calcium and increased sensitivity to agonists.