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

Atherosclerosis. 2005 Oct;182(2):277-85. doi: 10.1016/j.atherosclerosis.2005.03.001. Epub 2005 Mar 28.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antioxidants / metabolism*
  • Arachidonic Acid / metabolism
  • Atherosclerosis / epidemiology
  • Atherosclerosis / metabolism*
  • Cholesterol, HDL / blood
  • Cholesterol, HDL / metabolism*
  • Dinoprost / analogs & derivatives
  • Dinoprost / metabolism
  • Humans
  • Lipid Peroxides / metabolism
  • Lipoproteins, LDL / metabolism
  • Male
  • Middle Aged
  • Oxidative Stress / physiology*
  • Phenotype
  • Risk Factors
  • Triglycerides / blood*


  • Antioxidants
  • Cholesterol, HDL
  • Lipid Peroxides
  • Lipoproteins, LDL
  • Triglycerides
  • oxidized low density lipoprotein
  • 8-epi-prostaglandin F2alpha
  • Arachidonic Acid
  • Dinoprost