Normal high density lipoprotein inhibits three steps in the formation of mildly oxidized low density lipoprotein: step 1

Apolipoprotein A-I (apoA-I) and an apoA-I peptide mimetic removed seeding m olecules from human low density Lipoprotein (LDL) and rendered the LDL resi stant to oxidation by human artery wall cells. The apoA-I-associated seedin g molecules included hydroperoxyoctadecadienoic acid (HPODE) and hydroperox yeicosatetraenoic acid (HPETE), LDL from mice genetically susceptible to fa tty streak lesion formation tvas highly susceptible to oxidation by artery wall cells and tvas rendered resistant to oxidation after incubation with a poA-I in vitro. Injection of apoA-I (but not apoA-II or murine serum albumi n) into mice rendered their LDL resistant to oxidation within 3 h, Infusion of apoA-I into humans rendered their LDL resistant to oxidation within 6 h , We conclude that 1) oxidation of LDL by artery wall cells requires seedin g molecules that include HPODE and HPETE; 2) LDL from mice genetically susc eptible to atherogenesis is more readily oxidized by artery wall cells; and 3) normal HDL and its components can remove or inhibit the activity of Lip ids in freshly isolated LDL that are required for oxidation by human artery wall cells.