Clinical studyEnhanced oxidative susceptibility and reduced antioxidant content of metabolic precursors of small, dense low-density lipoproteins☆
Section snippets
Subjects
We studied 15 healthy normolipidemic adult volunteers, 9 with the large, buoyant LDL phenotype and 6 with the small, dense LDL phenotype, as determined by nondenaturing gradient gel electrophoresis and analytical ultracentrifugation of plasma (22). We excluded subjects with a plasma triglyceride concentration greater than 250 mg/dL, a plasma total cholesterol concentration greater than 250 mg/dL, or those who used dietary supplements or drugs known to alter plasma lipid or lipoprotein. Subjects
Oxidation properties of lipoprotein subfractions
In both groups of subjects (those with either the large, buoyant or the small, dense LDL phenotype), oxidative susceptibility increased significantly from intermediate-density lipoproteins to buoyant LDL to dense LDL particles Figure 1, Figure 2. Oxidative susceptibility as determined by the parinaric acid test was greater in intermediate-density lipoproteins from subjects with the small, dense LDL versus the large, buoyant LDL phenotype (Figure 2).
Antioxidant content and chemical composition of lipoprotein subfractions
As shown in Figure 3, antioxidant
Discussion
Small, dense LDL particles are more susceptible to oxidation than large, buoyant LDL particles (9–18). This property has been proposed to contribute to the increased disease risk associated with the dense LDL phenotype. In this study, we sought to determine whether these differences in oxidative susceptibility are related to differences in the oxidation properties of the presumed intermediate-density lipoprotein precursors of large, buoyant and small, dense LDL. We tested this hypothesis by
References (41)
- et al.
Identification of multiple subclasses of plasma low density lipoproteins in normal subjects
J Lipid Res
(1982) - et al.
Heterogeneity of serum low density lipoproteins in normal human subjects
J Lipid Res
(1981) - et al.
Role of plasma triglyceride in the regulation of plasma low density lipoprotein (LDL) subfractionsrelative contribution of small, dense LDL to coronary heart disease risk
Atherosclerosis
(1994) - et al.
Variations in oxidative susceptibility among six low density lipoprotein subfractions of varying size and density
Atherosclerosis
(1992) - et al.
Dense low density lipoprotein subspecies with diminished oxidative resistance predominate in combined hyperlipidemia
J Lipid Res
(1993) - et al.
Susceptibility of small, dense low-density lipoproteins to oxidative modification in subjects with the atherogenic lipoprotein phenotype pattern B
Am J Med
(1993) - et al.
Enhanced oxidative susceptibility of the surface monolayer in small, dense LDL may contribute to differences in copper-induced oxidation among LDL density subfractions
J Lipid Res
(1995) - et al.
Autoantibodies against malondialdehyde-modified LDL are elevated in subjects with an LDL subclass pattern B
Atherosclerosis
(1995) - et al.
Identification of multiple subclasses of plasma low density lipoproteins in normal humans
J Lipid Res
(1982) - et al.
Autooxidation of human low density lipoproteinloss of polyunsaturated fatty acids and vitamin E and generation of aldehydes
J Lipid Res
(1987)
Determination of coenzyme Q10, alpha-tocopherol and cholesterol in biological samples by coupled-column liquid chromatography with coulometric and ultraviolet detection
J Chromatog
A modification of the Lowry procedure to simplify protein determination in membrane and lipoprotein samples
Ann Biochem
Phosphorus assay in column chromatography
J Biol Chem
The determination of total cholesterol in serum by gas-liquid chromatography compared with two other methods
Clin Chim Acta
Discrete subspecies of human LDL are heterogeneous in their interaction with the cellular LDL receptor
J Lipid Res
Hepatic lipase and lipoprotein lipase are not major determinants of the low density lipoprotein subclass pattern in human subjects with coronary heart disease
Atherosclerosis
LDL oxidizability by copper correlates to its initial ubiquinol-10, and polyunsaturated fatty acid content
FEBS lett
Content of antioxidants, preformed lipid hydroperoxides, and cholesterol as predictors of the susceptibility of human LDL to metal ion-dependent and -independent oxidation
J Lipid Res
Triglycerides and atherogenic lipoproteinsrationale for lipid management
Am J Med
Low density lipoprotein subclass and risk of myocardial infarction
JAMA
Cited by (0)
- ☆
This research was supported by NIH grants DK02456, HL 30086 and HL 54606 and by the US Department of Energy under contract no. DE-AC03–76SF00098. Dr. Rizzo was the recipient of grants from the Italian Council of Research (Consiglio Nazionale delle Ricerche), Rome, Italy, and from the International Atherosclerosis Society, Houston, Texas.