Effect of hypochlorite-modified low-density and high-density lipoproteins on intracellular Ca2+ and plasma membrane Ca2+-ATPase activity of human platelets

The presence of hypochlorite-modified lipoproteins in atherosclerotic lesio ns suggests that HOCl, a naturally occurring oxidant formed by the myeloper oxidase-catalyzed reaction of H2O2 and Cl-, is a candidate for generation o f modified lipoproteins in vivo. We have previously demonstrated that Cu2+- oxidized LDL inhibits platelet plasma membrane Ca2+-ATPase (PMCA) in isolat ed membranes and causes an increase in cytosolic Ca2+ in resting whole plat elets. However, Cu2+-oxidized LDL may not be identical in structure and fun ction to the physiologically modified lipoprotein. Since platelet function may be affected by native and modified lipoproteins, the effect of HOCl-mod ified LDL and HDL3 on platelet PMCA and on the free intracellular Ca2+ conc entration ([Ca2+](i)) of whole platelets has been investigated. We demonstr ate that in contrast to Cu2+-oxidized LDL, HOCl-modified LDL and HDL, stimu late platelet PMCA activity in isolated membranes and that this effect resu lts in a decrease of [Ca2+](i) in vivo. Thus, HOCl-oxidation produces modif ied lipoproteins with the potential for altering platelet function and with properties different from those of the Cu2+-oxidized counterparts. (C) Har court Publishers Ltd 1999.