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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:638.)
© 2002 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Opposite Effects of Plasma From Human Apolipoprotein A-II Transgenic Mice on Cholesterol Efflux From J774 Macrophages and Fu5AH Hepatoma Cells

Natalie Fournier; Anne Cogny; Véronique Atger; Danièle Pastier; Dominique Goudouneche; Antonino Nicoletti; Nicole Moatti; Jean Chambaz; Jean-Louis Paul; Athina-Despina Kalopissis

From the Laboratoire de Biochimie (N.F., D.G., N.M., J.-L.P.), Faculté des Sciences Pharmaceutiques, Châtenay-Malabry; Laboratoire de Biochimie (N.F., A.C., V.A., N.M., J.-L.P.), Hôpital Européen Georges Pompidou, AP-HP, Paris; U505 INSERM (D.P., J.C., A.-D.K.), Université Pierre et Marie Curie, Centre de Recherche des Cordeliers, Paris; and U430 INSERM (A.N.), Hôpital Broussais, AP-HP, Paris, France.

Correspondence to Dr N. Fournier, Laboratoire de Biochimie, Faculté des Sciences Pharmaceutiques, 5 rue JB Clément, 92296 Châtenay-Malabry, France. E-mail natalie_fournier{at}yahoo.fr

Overexpression of human apolipoprotein A-II (hapo A-II) in transgenic mice (hAIItg mice) induced marked hypertriglyceridemia and low levels of plasma high density lipoprotein (HDL) with a high hapo A-II content. We sought to determine whether cholesterol efflux to plasma and HDL from these mice would be affected. In the Fu5AH cell system, plasma from hAIItg mice induced a markedly lower cholesterol efflux than did control plasma, in accordance with the dependence of efflux on HDL concentration. Moreover, HDLs from hAIItg mice were less effective acceptors than were control HDLs. In the J774 macrophage cell system, pretreatment with cAMP, which upregulates ATP binding cassette transporter 1, induced a marked increase in the efflux to hAIItg plasma as well as to purified hapo A-I and hapo A-II, whereas it had no effect on cholesterol efflux to control plasma. A strong positive correlation was established between percent cAMP stimulation of efflux and plasma hapo A-II concentration. The cAMP stimulation of efflux to hAIItg mouse plasma may be linked to the presence of pre-ß migrating HDL containing hapo A-II. Thus, despite lower HDL and apolipoprotein A-I contents, the increased ability of plasma from hAIItg mice to extract cholesterol from macrophage-like cells may have an antiatherogenic influence.

Key Words: human apolipoprotein A-II transgenic mice • Fu5AH rat hepatoma cells • J774 mouse macrophages • cholesterol efflux • ATP binding cassette transporter 1

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