A normotriglyceridemic, low HDL-cholesterol phenotype is characterised by elevated oxidative stress and HDL particles with attenuated antioxidative activity.
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.


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.
Kontush
Anatol
A
Dyslipoproteinemia 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
de Faria
Eliana Cotta
EC
Chantepie
Sandrine
S
Chapman
M John
MJ
D000328:Adult; D000975:Antioxidants / Q000378:metabolism*; D016718:Arachidonic Acid / Q000378:metabolism; D050197:Atherosclerosis / Q000453:epidemiology / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000097:blood / Q000378:metabolism*; D015237:Dinoprost / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D008054:Lipid Peroxides / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology*; D010641:Phenotype; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood*
D000975:Antioxidants; D008076:Cholesterol, HDL; D008054:Lipid Peroxides; D008077:Lipoproteins, LDL; D014280:Triglycerides; C099252:oxidized low density lipoprotein; C075750:8-epi-prostaglandin F2alpha; D016718:Arachidonic Acid; D015237:Dinoprost