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Originally published In Press as doi:10.1194/jlr.M600309-JLR200 on February 28, 2007

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Journal of Lipid Research, Vol. 48, 1396-1401, June 2007
Copyright © 2007 by American Society for Biochemistry and Molecular Biology

Patient-Oriented Research

Inability of HDL from abdominally obese subjects to counteract the inhibitory effect of oxidized LDL on vasorelaxation

Laurence Perségol*,{dagger}, Bruno Vergès*,{dagger},§, Philippe Gambert*,{dagger} and Laurence Duvillard1,*,{dagger}

* Institut National de la Santé et de la Recherche Médicale U866, Dijon F-21000, France
{dagger} University of Burgundy, Institut Fédératif de Recherche 100, Dijon F-21000, France
§ Department of Endocrinology and Metabolic Diseases, Centre Hospitalier Universitaire Dijon Bocage Hospital, Dijon F-21000, France

Published, JLR Papers in Press, February 28, 2007.

1 To whom correspondence should be addressed. e-mail: laurence.duvillard{at}chu-dijon.fr


ABSTRACT

Abdominal obesity is associated with a decreased plasma concentration of HDL cholesterol and with qualitative modifications of HDL, such as triglyceride enrichment. Our aim was to determine, in isolated aorta rings, whether HDL from obese subjects can counteract the inhibitory effect of oxidized low density lipoprotein (OxLDL) on endothelium-dependent vasodilation as efficiently as HDL from normolipidemic, lean subjects. Plasma triglycerides were 74% higher (P < 0.005) in obese subjects compared with controls, and apolipoprotein A-I (apoA-I) and HDL cholesterol concentrations were 12% and 17% lower (P < 0.05), respectively. HDL from control subjects significantly reduced the inhibitory effect of OxLDL on vasodilation [maximal relaxation (Emax) = 82.1 ± 8.6% vs. 54.1 ± 8.1%; P < 0.0001], but HDL from obese subjects had no effect (Emax = 47.2 ± 12.5% vs. 54.1 ± 8.1%; NS). In HDL from abdominally obese subjects compared with HDL from controls, the apoA-I content was 12% lower (P < 0.05) and the triglyceride-to-cholesteryl ester ratio was 36% higher (P = 0.08)). Emax(OxLDL + HDL) was correlated with HDL apoA-I content and triglyceride-to-cholesteryl ester ratio (r = 0.36 and r = –0.38, respectively; P < 0.05). We conclude that in abdominally obese subjects, the ability of HDL to counteract the inhibitory effect of OxLDL on vascular relaxation is impaired. This could contribute to the increased cardiovascular risk observed in these subjects.

Supplementary key words obesity • high density lipoprotein • oxidized low density lipoprotein • triglycerides • apolipoprotein A-I

Abbreviations: apoA-I, apolipoprotein A-I; Emax, maximal relaxation; eNOS, endothelial nitric oxide synthase; HOMA, homeostasis model assessment; NO, nitric oxide; OxLDL, oxidized low density lipoprotein; PAF-AH, platelet-activated factor-acetyl hydrolase; PON, paraoxonase






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Copyright © 2007 by the American Society for Biochemistry and Molecular Biology.