OXIDIZED LOW-DENSITY-LIPOPROTEIN INHIBITS PLATELET PLASMA-MEMBRANE CA2-ATPASE()

Oxidized low density lipoprotein (LDL) has been shown to enhance plate let activation. Since platelet activation is accompanied by an increas e in cytosolic calcium, the effects of oxidized LDL on plasma membrane Ca2+- ATPase, plasma membrane fluidity and cytoplasmic calcium were s tudied in human platelets and purified platelet plasma membranes. Our results demonstrate that oxidized LDL, but not native LDL, inhibits th e activity of Ca2+-ATPase in purified platelet plasma membranes (P < 0 .01). Addition of the free radical scavenger a-tocopherol had no effec t on the ability of oxidized LDL to inhibit the Ca2+-ATPase. An increa sed cytoplasmic calcium level in whole platelets was induced by oxidiz ed LDL (P < 0.01), indicating that the plasma membrane Ca2+-extrusion pump may also be inhibited in vivo by oxidized LDL, although other mec hanisms 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 trimet hylammonium diphenylhexatriene (TMA-DPH) anisotropy, oxidized LDL does not affect the Ca2+-ATPase by grossly changing the membrane environme nt. The present results suggest that exposure of platelets to oxidized LDL causes inhibition of the plasma membrane Ca2+-ATPase which contri butes to the observed increase in cytoplasmic calcium and increased se nsitivity to agonists.