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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:1711.)
© 2005 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Genes of Cholesterol Metabolism in Human Atheroma

Overexpression of Perilipin and Genes Promoting Cholesterol Storage and Repression of ABCA1 Expression

Fabien Forcheron; Liliana Legedz; Guiletta Chinetti; Patrick Feugier; Dominique Letexier; Giampierro Bricca; Michel Beylot

From INSERM U499 (F.F.), Faculté Laennec, UCB Lyon I, Lyon, France; EA 3740 (L.L.), Faculté Laennec UCB Lyon I, Lyon, France; INSERM UR545 (G.C.), Institut Pasteur de Lille, Lille, France; Hospices Civils de Lyon (P.F.), Lyon, France; INSERM U499 (D.L.), UCB Lyon I, Lyon, France; EA 3740 (G.B.), UCB Lyon I, Lyon, France; INSERM U499 (M.B.), UCB Lyon I, Lyon, France.

Correspondence to M. Beylot, INSERM U499, Faculté RTH Laennec, Rue G Paradin, 69008 Lyon, France. E-mailbeylot{at}laennec.univ-lyon1.fr

Objective— Accumulation of cholesterol in foam cells of atheroma plaques depends on the balance between uptake and efflux of cholesterol. It may also depend on proteins surrounding lipid droplets, adipophilin, and perilipins. They favor triglyceride storage in adipocytes and could play a similar role for cholesterol in atheroma.

Methods and Results— We measured in human atheroma and nearby macroscopically intact tissue (MIT) the expression of perilipin, adipophilin, and regulatory factors of cholesterol metabolism. We identified perilipin A in human arterial wall. Its expression was largely increased in atheroma compared with MIT, and perilipin was present in macrophages and vascular smooth muscle cells. Adipophilin, ACAT1, and CD36 were also overexpressed in atheroma. mRNA levels of low-density lipoprotein receptor, 3-hydroxy-3-methylglutaryl coenzyme A reductase, and SREBP-2 were unchanged. With respect to efflux of cholesterol, the mRNA levels of NCEH and ABCA-1 were unchanged, whereas CLA-1 mRNA was slightly higher in atheroma. Importantly, immunoblotting of ABCA-1 showed a dramatic decrease of ABCA1 protein, the key molecule of cholesterol efflux, in atheroma compared with MIT.

Conclusion— We show the presence and induction of perilipin in atheroma. This overexpression and the coordinated modifications of expression of key regulatory factors for cholesterol metabolism could favor cholesterol accumulation.

We measured in human atheroma and nearby tissue the expression of perilipin and ADRP, which are key factors of cholesterol metabolism. We show the presence and induction of perilipin in atheroma and coordinated modifications of the expression of regulatory factors for cholesterol metabolism that favor its uptake and storage and reduce its efflux.

Key Words: atherosclerosis • genes • lipids • macrophages • smooth muscle cells

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