CORE LIPID STRUCTURE IS A MAJOR DETERMINANT OF THE OXIDATIVE RESISTANCE OF LOW-DENSITY-LIPOPROTEIN

The influence of thermally induced changes in the lipid core structure on the oxidative resistance of discrete, homogeneous low density lipo protein (LDL) subspecies (d, 1.0297-1.0327 and 1.0327-1.0358 g/ml) has been evaluated. The thermotropic transition of the LDL lipid core at temperatures between 15 degrees C and 37 degrees C, determined by diff erential scanning calorimetry, exerted significant effects on the kine tics of copper-mediated LDL oxidation expressed in terms of intrinsic antioxidant efficiency (lag time) and diene production rate. Thus, the temperature coefficients of oxidative resistance and maximum oxidatio n rate showed break points at the core transition temperature. Tempera ture-induced changes in copper binding were excluded as the molecular basis of such effects, as the saturation of LDL with copper was identi cal below and above the core transition. At temperatures below the tra nsition, the elevation in lag time indicated a greater resistance to o xidation, reflecting a higher degree of antioxidant protection. This e ffect can be explained by higher motional constraints and local antiox idant concentrations, the latter resulting from the freezing out of an tioxidants from crystalline domains of cholesteryl esters and triglyce rides. Below the transition temperature, the conjugated diene producti on rate was decreased, a finding that correlated positively with the a verage size of the cooperative units of neutral lipids estimated from the calorimetric transition width. The reduced accessibility and struc tural hindrance in the cluster organization of the core lipids therefo re inhibits peroxidation. Our findings provide evidence for a distinct effect of the dynamic state of the core lipids on the oxidative susce ptibility of LDL and are therefore relevant to the atherogenicity of t hese cholesterol-rich particles.