Role of plasmalogens in the enhanced resistance of LDL to copper-induced oxidation after LDL apheresis

Extracorporeal reduction of plasma low density lipoproteins (LDLs) by LDL a pheresis was shown to attenuate the proatherogenic influences of LDL, such as impairment of vasodilation and increased monocyte adhesion to the endoth elium. In 16 patients with familial hypercholesterolemia, we analyzed wheth er LDL apheresis by the heparin precipitation procedure affected the oxidat ive resistance of LDL. Plasma LDL cholesterol concentrations were reduced b y 65% after the apheresis. The lag time of copper-mediated LDL oxidation wa s increased from 103 to 117 minutes (P<0.0005). The LDL contents of alpha-t ocopherol and beta-carotene, as well as the ratio of monounsaturated to pol yunsaturated fatty acids in LDL, were not altered. However, the LDL apheres is induced a 15% increase in the LDL contents of plasmalogen phospholipids (P<0.0005), a class of ether phospholipids that were recently shown to prev ent lipid oxidation. The phosphatidylcholine (PC) to lysoPC ratio was eleva ted by 16% after the apheresis (P<0.0005). The percent increase in LDL plas malogen phospholipids showed a close association with the increased lag tim e after apheresis (P<0.0005). The LDL plasmalogen contents of the blood sam ples from patients and from normolipidemic donors were also positively rela ted to the lag time (P<0.005). In vitro loading of LDL with plasmalogen pho spholipids resulted in a prolongation of the lag time and an increase in th e PC/lysoPC ratio. In conclusion, the rapid rise in LDL contents of plasmal ogen phospholipids most probably causes the increase in lag time after LDL apheresis. Plasmalogens appear to play an important role in the oxidation r esistance of LDL in vivo.