DIFFERENCES IN LDL SUBSPECIES INVOLVE ALTERATIONS IN LIPID-COMPOSITION AND CONFORMATIONAL-CHANGES IN APOLIPOPROTEIN-B

In order to investigate causes of variability in low density lipoprote in (LDL) particle size, we have assessed LDL composition in plasma fro m 66 subjects, each with a single LDL band, by 2-16% gradient gel elec trophoresis, with a total of eight discrete sizes (LDL-1 to LDL-8). Li poprotein concentrations were analyzed by standard methods; specific p roteins were assessed by immunoassay and electrophoresis. Results show ed decreased anhydrous molecular weight with size (2.67 +/- 0.07 x 10( 6) to 1.78 +/- 0.19 x 10(6)), along with decreased relative content fo r cholesteryl ester (41.5% to 24.3%), free cholesterol (10.1% to 4.6%) , and phospholipid (23.7% to 18.9%), and increased triglyceride (4.1% to 21.0%) and protein (20.5% to 31.2%) content. As LDL size decreased, tile ratio of surface cholesterol to phospholipid decreased from 0.53 to 0.29, and tile fraction of surface area covered by lipid decreased from 0.74 to 0.47. Moreover, core volume decreased with size from 24. 2 Angstrom(3) x 10(5) to 15.9 Angstrom(3) x 10(5), and the ratio of su rface-to-core lipids fell from 0.59 to 0.46. Based on surface pressure s of 30 mN/m, the area covered by surface lipid was calculated to rang e from 6.45 Angstrom(2) x 10(4) in the largest LDL, to 3.10 Angstrom(2 ) x 10(4) in tile smallest, Computer modeling indicates that alteratio ns in the tertian; structure of apoB-100 are required to account for s urface changes. The estimated core surface area requiring coverage by apoB increased with decreasing particle size from 2.26 Angstrom(2) x 1 0(4) to 3.46 Angstrom(2) x 10(4). To accommodate coverage of increasin g relative surface area associated with decreasing size, apoB thicknes s at the interface was calculated to decrease from approximately 25 An gstrom to 16 Angstrom. Such conformational changes in apoB may alter e xposed epitopes, possibly causing changes in LDL receptor binding affi nity and resistance to oxidation.