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Originally published In Press as doi:10.1194/jlr.M700510-JLR200 on December 5, 2007

Papers In Press, published online ahead of print March 1, 2008
J. Lipid Res., doi:10.1194/jlr.M700510-JLR200
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Journal of Lipid Research, Vol. 49, 635-643, March 2008
Copyright © 2008 by American Society for Biochemistry and Molecular Biology

Cellular SR-BI and ABCA1-mediated cholesterol efflux are gender-specific in healthy subjectsboxs

Giovanna Catalano*,{dagger}, Emilie Duchene*,{dagger},§, Zélie Julia*,{dagger}, Wilfried Le Goff*,{dagger}, Eric Bruckert§, M. John Chapman*,{dagger} and Maryse Guerin1,*,{dagger}

* Institut National de la Santé et de la Recherche Médicale, UMR_S551, Dyslipoproteinemia and Atherosclerosis, Paris, France
{dagger} Université Pierre et Marie Curie-Paris 6, Unité Mixte de Recherche S551, Paris, France
§ Department of Endocrinology, Hôpital Assistance Publique-Hopitaux de Paris, Hopital de la Pitie-Salpetriere, Paris, France

boxs The online version of this article (available at http://www.jlr.org) contains supplementary data in the form of one figure.

Published, JLR Papers in Press, December 5, 2007.

1 To whom correspondence should be addressed. e-mail: mguerin{at}chups.jussieu.fr

We evaluated the impact of gender differences in both the quantitative and qualitative features of HDL subspecies on cellular free cholesterol efflux through the scavenger receptor class B type I (SR-BI), ABCA1, and ABCG1 pathways. For that purpose, healthy subjects (30 men and 26 women) matched for age, body mass index, triglyceride, apolipoprotein A-I, and high density lipoprotein-cholesterol (HDL-C) levels were recruited. We observed a significant increase (+14%; P < 0.03) in the capacity of whole sera from women to mediate cellular free cholesterol efflux via the SR-BI-dependent pathway compared with sera from men. Such enhanced efflux capacity resulted from a significant increase in plasma levels of large cholesteryl ester-rich HDL2 particles (+20%; P < 0.04) as well as from an enhanced capacity (+14%; P < 0.03) of these particles to mediate cellular free cholesterol efflux via SR-BI. By contrast, plasma from men displayed an enhanced free cholesterol efflux capacity (+31%; P < 0.001) via the ABCA1 transporter pathway compared with that from women, which resulted from a 2.4-fold increase in the plasma level of preβ particles (P < 0.008). Moreover, in women, SR-BI-mediated cellular free cholesterol efflux was significantly correlated with plasma HDL-C (r = 0.72, P < 0.0001), whereas this relationship was not observed in men. In conclusion, HDL-C level may not represent the absolute indicator of the efficiency of the initial step of the reverse cholesterol transport.

Supplementary key words ATP binding cassette G1 • scavenger receptor class B type I • high-density-lipoprotein






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