Oxygenation of lipoproteins by mammalian lipoxygenases

Abstract

Oxidative modification converts low‐density lipoprotein (LDL) into its atherogenic form and appears to be a necessary precondition for LDL uptake by macrophages during foam cell formation. Cellular lipoxygenases have been implicated in this process. We studied the interaction of purified mammalian lipoxygenases with human LDL in vitro and found that the arachidonate 15‐lipoxygenases of rabbit and man are capable of oxygenating lipoproteins as indicated by oxygen uptake and by the formation of thiobarbituric‐acid‐reactive substances. Furthermore, oxygenated polyenoic fatty acids, such as 13‐hydro(pero)xy‐9Z,11E‐octadecadienoic acid and 15‐hydro(pero)xy‐5,8,11,13(Z,Z,Z,E)‐eicosatetraenoic acid were detected in the lipid compartment of various lipoproteins classes after lipoxygenase treatment. More than 90% of the oxygenated polyenoic fatty acids were found in the ester‐lipid fraction, particularly in the cholesterol esters, whereas only small amounts of free hydro(pero)xy polyenoic fatty acids were detected. Lipoxygenase‐catalyzed oxygenation of LDL is not restricted to the lipid compartment but also leads to a cooxidative modification of the apoproteins as indicated by changes in the electrophoretic mobility and by the formation of carbonyl derivatives of amino acid side chains. The possible biological significance of lipoxygenase‐induced oxidative modification of lipoproteins in the pathogenesis of atherosclerosis is discussed.