A novel function of lipoprotein a as a preferential carrier of oxidized phospholipids in human plasma

Oxidized phospholipids (OxPLs) on apolipoprotein B-100 (apoB-100) particles are strongly associated with lipoprotein a (Lpa). In this study, we evaluated whether Lpa is preferentially the carrier of OxPL in human plasma. The content of OxPL on apoB-100 particles was measured with monoclonal antibody E06, which recognizes the phosphocholine (PC) headgroup of oxidized but not native phospholipids. To assess whether OxPLs were preferentially bound by Lpa as opposed to other lipoproteins, immunoprecipitation and ultracentrifugation experiments, in vitro transfer studies, and chemiluminescent ELISAs were performed. Immunoprecipitation of Lpa from human plasma with an apolipoprotein a (apoa)-specific antibody demonstrated that more than 85% of E06 reactivity (i.e., OxPL) coimmunoprecipitated with Lpa. Ultracentrifugation experiments showed that nearly all OxPLs were found in fractions containing apoa, as opposed to other apolipoproteins. In vitro transfer studies showed that oxidized LDL preferentially donates OxPLs to Lpa, as opposed to LDL, in a time- and temperature-dependent manner, even in aqueous buffer. Approximately 50% of E06 immunoreactivity could be extracted from isolated Lpa following exposure of plasma to various lipid solvents. These data demonstrate that Lpa is the preferential carrier of PC-containing OxPL in human plasma. This unique property of Lpa suggests novel insights into its physiological function and mechanisms of atherogenicity.