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

Glutaraldehyde treatment of ¹²⁵I-labeled low density lipoprotein (¹²⁵I-native-LDL) produced a modified LDL (¹²⁵I-glut-LDL) with a molecular weight of 10 × 10⁶ or more. Malondialdehyde treatment of ¹²⁵I-native-LDL produced a product (¹²⁵I-MDA-LDL) with a molecular weight not appreciably different from that of the original lipoprotein. However, the electrophoretic mobility of MDA-LDL indicated a more negative charge than native-LDL. ¹²⁵I-MDA-LDL was degraded by two processes: a high-affinity saturable process with maximal velocity at 10-15 μg 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 μg of protein per ml. After exposure of native-LDL to 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.