Malondialdehyde alteration of low density lipoproteins leads to cholesteryl ester accumulation in human monocyte-macrophages

Abstract

Glutaraldehyde treatment of 125I-labeled low density lipoprotein (125I-native-LDL) produced a modified LDL (125I-glut-LDL) with a MW of 10 .times. 106 or more. Malondialdehyde treatment of 125I-native-LDL produced a product (125I-MDA-LDL) with a MW not appreciably different from that of the original lipoprotein; the electrophoretic mobility of MDA-LDL indicated a more negative charge than native-LDL. 125I-MDA-LDL was degraded by a high-affinity saturable process with maximal velocity at 10-15 .mu.g of protein per ml and a slower, nonsaturable process. The degradation of 125I-MDA-LDL was readily inhibited by increasing concentrations of nonradioactive MDA-LDL, but was not inhibited by acetylated LDL or native-LDL even at concentrations as high as 1600 .mu.g of protein per ml. After exposure of native-LDL to [human] blood platelet aggregation and release in vitro, 1.73 .+-. 0.19 nmol of malondialdehyde per mg of LDL Protein was bound to the platelet-modified-LDL. No detectable malondialdehyde was recovered from native-LDL that had been treated identically except that the platelets were omitted from the reaction mixture. After incubation with glut-LDL, MDA-LDL or platelet-modified-LDL for 3 days, human monocyte-macrophages showed a dramatic increase in cholesteryl ester content; the cholesteryl ester content of cells incubated with the same concentration of native-LDL did not. Modification of native-LDL may be a prerequisite to the accumulation of cholesteryl esters within the cells of the atherosclerotic reaction. One modification of LDL in vivo may result from malondialdehyde which is released from blood platelets or is produced by lipid peroxidation at the site of arterial injury.