on June 16, 2005
Published online before print June 16, 2005, doi: 10.1161/01.ATV.0000174123.19103.52
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Submitted on January 29, 2004
Accepted on June 2, 2005
Genes of Cholesterol Metabolism in Human Atheroma. Overexpression of Perilipin and Genes Promoting Cholesterol Storage and Repression of ABCA1 Expression
Fabien Forcheron ;
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.
* To whom correspondence should be addressed. E-mail: beylot{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 acyl-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.
Key words: atherosclerosis • genes • lipids • macrophages • smooth muscle cells
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