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Updated: Aug 16, 2026
Cell-free Biochemical Fluorometric Enzymatic Assay for High-throughput Measurement of Lipid Peroxidation in High Density Lipoprotein
Published on: October 12, 2017
A normotriglyceridemic, low HDL-cholesterol phenotype is characterised by elevated oxidative stress and HDL particles
Anatol Kontush1, Eliana Cotta de Faria, Sandrine Chantepie
1Dyslipoproteinemia and Atherosclerosis Research Unit (U.551), National Institute for Health and Medical Research (INSERM), Hôpital de la Pitié, 83 boulevard de l'Hôpital, 75651 Paris Cedex 13, France. kontush@chups.jussieu.fr
Insights
Low high-density lipoprotein-cholesterol (HDL-C) is linked to increased oxidative stress and dysfunctional HDL particles. These HDL particles have reduced antioxidant capacity due to altered composition, contributing to cardiovascular risk.
Area of Science:
- Cardiovascular Science
- Lipid Metabolism
- Oxidative Stress Research
Background:
- Low levels of high-density lipoprotein-cholesterol (HDL-C) are common in individuals with premature atherosclerosis.
- The role of oxidative stress and HDL particle dysfunction in this increased cardiovascular risk is not fully understood.
Purpose of the Study:
- To investigate whether high cardiovascular risk in low HDL-C subjects is associated with elevated oxidative stress.
- To determine if low HDL-C is linked to biologically dysfunctional HDL particles.
Main Methods:
- Measured systemic oxidative stress using plasma 8-isoprostanes.
- Isolated HDL subfractions via density gradient ultracentrifugation.
- Assessed the specific antioxidative activity (sAA) of HDL subfractions.
Main Results:
- Subjects with low HDL-C exhibited a 2.3-fold increase in plasma 8-isoprostanes compared to controls.
- Isolated HDL subfractions from low HDL-C subjects showed significantly reduced specific antioxidative activity (-21% to -43%).
- Altered HDL composition (triglyceride enrichment, cholesteryl ester depletion) correlated with reduced antioxidative function.
Conclusions:
- Low HDL-C is associated with heightened systemic oxidative stress.
- HDL particles in low HDL-C individuals possess diminished intrinsic antioxidative activity.
- This dysfunction in HDL is closely related to changes in its chemical composition.
Objective:
Low levels of high density lipoprotein-cholesterol (HDL-C) are highly prevalent in subjects presenting premature atherosclerosis. It is indeterminate as to whether high cardiovascular risk in low HDL-C subjects occurs concomitantly with elevated oxidative stress and/or with biologically dysfunctional HDL particles.
Methods And Results:
Systemic oxidative stress (as plasma 8-isoprostanes) was 2.3-fold elevated (p<0.05) in normocholesterolemic, normotriglyceridemic, normoglycemic low HDL-C subjects (plasma HDL-C, <40 mg/dL; n=8) as compared to normolipidemic controls (n=15). HDL subfractions (HDL2b, 2a, 3a, 3b and 3c) isolated by density gradient ultracentrifugation from low HDL-C subjects displayed significantly lower (-21 to -43%, p<0.05) specific antioxidative activity (sAA; capacity to protect LDL from oxidation on a unit particle mass or on a particle number basis) as compared to controls. Altered chemical composition (core triglyceride enrichment, cholesteryl ester depletion) paralleled antioxidative dysfunction of HDL subfractions. Plasma 8-isoprostane levels negatively correlated with sAA of HDL subfractions and positively correlated with the total cholesterol/HDL-C ratio, which was significantly elevated in the low HDL-C phenotype.
Conclusions:
Low HDL-C subjects display elevated oxidative stress and possess HDL particle subspecies with attenuated intrinsic antioxidative activity which is intimately related to their altered chemical composition.
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