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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:756.)
© 2004 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Human Apolipoprotein A-IV Reduces Secretion of Proinflammatory Cytokines and Atherosclerotic Effects of a Chronic Infection Mimicked by Lipopolysaccharide

Delia Recalde; Maria A. Ostos; Edgar Badell; Angel-Luis Garcia-Otin; Josette Pidoux; Graciela Castro; Mario M. Zakin; Daniel Scott-Algara

From Unité d’Expression des Gènes Eucaryotes (D.R., M.A.O., A.-L.G.-O., J.P., M.M.Z.), Institut Pasteur, Paris, France; Unité de Génétique Mycobactérienne (E.B.), Institut Pasteur, Paris, France; U545 Inserm (G.C.), Institut Pasteur and Faculté de Pharmacie, Université Lille II, Lille, France; and Unité d’Immuno-Hématologie et d’Immunopathologie (D.S.-A.), Institut Pasteur, Paris, France.

Correspondence to D. Scott-Algara, Institut Pasteur, 28, rue du Docteur Roux, 75724 Paris Cedex 15, France. E-mail scott{at}pasteur.fr

Objective— Expression of human apolipoprotein (h-apo) A-IV in apoE-deficient (apoE₀) mice (h-apoA-IV/E₀) reduces susceptibility to atherosclerosis. Chronic infection mimicked by exposure to lipopolysaccharide (LPS) increases the size of atherosclerosis lesions in apoE₀ mice. Thus, we used h-apoA-IV/E₀ mice to determine whether h-apoA-IV plays a protective role after LPS administration.

Methods and Results— We injected apoE₀, h-apoA-IV/E₀, and C57Bl/6 (wild-type) mice intraperitoneally with either LPS or phosphate-buffered saline (PBS) every week for 10 weeks. Atherosclerotic lesions were significantly smaller in h-apoA-IV/E₀ mice treated with LPS than in their apoE₀ counterparts. The titers of IgG2a and IgG2b autoantibodies to oxidized low-density lipoprotein (LDL) were higher in the LPS-group of h-apoA-IV/E₀ mice than in apoE₀ mice, suggesting that the Th1 response is stronger in the presence of h-apoA-IV. Lymphocytes from the blood, liver, spleen, and thymus of h-apoA-IV/E₀ mice treated with LPS produced less IL-4, INF-, and TNF- proinflammatory cytokines than their apoE₀ counterparts. Furthermore, we demonstrated that recombinant h-apoA-IV blocks the LPS-induced stimulation of monocytes.

Conclusions— The expression of h-apoA-IV in apoE₀ mice reduces the susceptibility to atherogenesis and decreases the secretion of proinflammatory cytokines after LPS administration.

Key Words: apolipoproteins • atherosclerosis • inflammation • transgenic mice • lipopolysaccharide

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