This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 24/3/526    most recent 01.ATV.0000118276.87061.00v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kontush, A. Articles by Chapman, M. J. Search for Related Content PubMed PubMed Citation Articles by Kontush, A. Articles by Chapman, M. J. Related Collections Lipid and lipoprotein metabolism Oxidant stress

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:526.)
© 2004 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Antioxidative Activity of HDL Particle Subspecies Is Impaired in Hyperalphalipoproteinemia: Relevance of Enzymatic and Physicochemical Properties

Anatol Kontush; Eliana Cotta de Faria; Sandrine Chantepie; M. John Chapman

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.

Correspondence to Dr Anatol Kontush, INSERM Unité 551, Pavillon Benjamin Delessert, Hôpital de la Pitié, 83 boulevard de l’Hôpital, 75651 Paris Cedex 13, France. 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

This article has been cited by other articles:

				R. S. Rosenson, D. A. Wolff, A. L. Huskin, I. B. Helenowski, and A. W. Rademaker Fenofibrate Therapy Ameliorates Fasting and Postprandial Lipoproteinemia, Oxidative Stress, and the Inflammatory Response in Subjects With Hypertriglyceridemia and the Metabolic Syndrome Diabetes Care, August 1, 2007; 30(8): 1945 - 1951. [Abstract] [Full Text] [PDF]

				A. Kontush and M. J. Chapman Functionally Defective High-Density Lipoprotein: A New Therapeutic Target at the Crossroads of Dyslipidemia, Inflammation, and Atherosclerosis Pharmacol. Rev., September 1, 2006; 58(3): 342 - 374. [Abstract] [Full Text] [PDF]

				I. O. Ottestad, B. Halvorsen, T. R. Balstad, K. Otterdal, G. I. Borge, F. Brosstad, A. M. Myhre, L. Ose, M. S. Nenseter, and K. B. Holven Triglyceride-Rich HDL3 from Patients with Familial Hypercholesterolemia Are Less Able to Inhibit Cytokine Release or to Promote Cholesterol Efflux J. Nutr., April 1, 2006; 136(4): 877 - 881. [Abstract] [Full Text] [PDF]

				A. H.E.M. Klerkx, K. E. Harchaoui, W. A. van der Steeg, S. M. Boekholdt, E. S.G. Stroes, J. J.P. Kastelein, and J. A. Kuivenhoven Cholesteryl Ester Transfer Protein (CETP) Inhibition Beyond Raising High-Density Lipoprotein Cholesterol Levels: Pathways by Which Modulation of CETP Activity May Alter Atherogenesis Arterioscler. Thromb. Vasc. Biol., April 1, 2006; 26(4): 706 - 715. [Abstract] [Full Text] [PDF]

				B. Hansel, P. Giral, E. Nobecourt, S. Chantepie, E. Bruckert, M. J. Chapman, and A. Kontush Metabolic Syndrome Is Associated with Elevated Oxidative Stress and Dysfunctional Dense High-Density Lipoprotein Particles Displaying Impaired Antioxidative Activity J. Clin. Endocrinol. Metab., October 1, 2004; 89(10): 4963 - 4971. [Abstract] [Full Text] [PDF]

				D. M. Herrington and J. S. Parks Estrogen and HDL: All that Glitters Is not Gold Arterioscler. Thromb. Vasc. Biol., October 1, 2004; 24(10): 1741 - 1742. [Full Text] [PDF]