on January 22, 2004
Published online before print January 22, 2004, doi: 10.1161/01.ATV.0000118276.87061.00
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Submitted on September 17, 2003
Accepted on December 16, 2003
Antioxidative Activity of HDL Particle Subspecies Is Impaired in Hyperalphalipoproteinemia: Relevance of Enzymatic and Physicochemical Properties
Anatol Kontush *;
From the Dyslipoproteinemia and Atherosclerosis Research Unit (U.551) (A.K., S.C., M.J.C.), National Institute for Health and Medical Research (INSERM), Pavillon Benjamin Delessert, Hôpital de la Pitié, Paris, France; and the School of Medicine (E.C.d.F.), Campinas University Hospital, Campinas, Brazil.
* To whom correspondence should be addressed. E-mail: kontush{at}chups.jussieu.fr.
Objective--Hyperalphalipoproteinemia (HALP) is characterized by elevated plasma levels of high-density lipoprotein (HDL) particles with altered composition, metabolism, and function. The impact of such modification on antioxidative activities of HDL subfractions is indeterminate.
Methods and Results--Gradient fractionation revealed that buoyant HDL2b and 2a and small dense HDL3b and 3c levels were elevated up to 2.0-fold in HALP subjects (n=9; mean plasma HDL cholesterol, 79 mg/dL) with low hepatic lipase activity. HDL2a, 3a, 3b, and 3c displayed lower specific antioxidative activity (sAA) during low-density lipoprotein (LDL) oxidation (-15% to -86%, on a unit particle mass basis) than their normolipidemic counterparts (n=13). LDL oxidation was delayed by control HDL3a, 3b, and 3c (up to -79%) but specifically by HDL3c (-54%) in HALP. Paraoxonase activity was deficient in all HALP HDL subfractions. Paraoxonase, PAF-AH, and LCAT activities together accounted for 
50% of variation in sAA. Abnormal chemical composition of HDL3b and 3c (cholesterol-deficient, triglyceride-enriched) in HALP was associated with impaired sAA. Systemic oxidative stress (as plasma 8-isoprostanes) tended to be elevated (1.5-fold) in HALP and negatively correlated with sAA (as TBARS).
Conclusions--Intrinsic antioxidative activity of HDL subspecies is impaired in HALP, reflecting altered enzymatic and physicochemical properties.
Key words: oxidative stress • HDL particle heterogeneity • LDL oxidation • lipid hydroperoxides • atherosclerosis
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