Abstract
The size of LDL is usually reported as particle diameter, with the implicit assumption that it is a spherical particle. On the other hand, data obtained by cryoelectron microscopy and crystallographic analysis suggest that LDL shape may be discoid. We have investigated LDL particle geometry by combining data on LDL lipid composition with size measurement. The mean LDL diameter of 160 samples was measured by high-performance gel-filtration chromatography (HPGC), and particle volume was calculated from its lipid composition. Assuming a spherical shape, diameters calculated from volume correlated poorly with values obtained by HPGC (R(2) = 0.36). Assuming a discoid shape, particle height was calculated from volume and HPGC diameter. Diameter (20.9 +/- 0.5 nm) and height (12.1 +/- 0.8 nm) were not significantly related to each other (r = 0.14, P = 0.09) and accounted for 23% and 77%, respectively, of the variation in particle volume. In multivariate regression models, LDL core lipids were the main determinants of height (R(2) = 0.83), whereas free cholesterol in the shell, which contributes only 5-9% to LDL mass, was the main determinant of diameter (R(2) = 0.54). We conclude that combined data from composition and size measurements are compatible with a discoid particle shape and propose a structural model for LDL in which free cholesterol plays a major role in determining particle shape and diameter.
Highlights
The size of LDL is usually reported as particle diameter, with the implicit assumption that it is a spherical particle
If LDL is a spherical particle, its diameter can be calculated from particle volume and the values obtained should be in good agreement with the values obtained by direct measurement
Reconciliation of this discrepancy between direct size measurement and calculated values was obtained by assuming cylindrical particle geometry, necessitating the use of two parameters to describe particle size
Summary
The size of LDL is usually reported as particle diameter, with the implicit assumption that it is a spherical particle. 954 Journal of Lipid Research Volume 45, 2004 of particles varying in density, size, composition, and other physicochemical properties This heterogeneity has clinical significance in that LDL subspecies differ in their metabolic behavior and pathologic roles [reviewed by Berneis and Krauss [1]]. Several techniques can be used to measure LDL size and size distribution, such as electron microscopy of negatively stained lipoproteins [9], photon correlation spectroscopy using light-scattering equipment [10], proton nuclear magnetic resonance spectroscopy [11,12,13], highperformance gel-filtration chromatography (HPGC) [14, 15], and nondenaturing polyacrylamide gradient gel electrophoresis (GGE) The latter technique has been most widely used in clinical and epidemiological studies. It has a very high resolution, enabling the separation of up to Abbreviations: apoB-100, apolipoprotein B-100; CE, cholesteryl ester; FC, free (unesterified) cholesterol; GGE, gradient gel electrophoresis; HPGC, high-performance gel-filtration chromatography; IDL, intermediate density lipoprotein; PL, phospholipid; TG, triglyceride
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