RGD Reference Report - Genes of cholesterol metabolism in human atheroma: overexpression of perilipin and genes promoting cholesterol storage and repression of ABCA1 expression.

General

Genes of cholesterol metabolism in human atheroma: overexpression of perilipin and genes promoting cholesterol storage and repression of ABCA1 expression.
Authors:	Forcheron, F Legedz, L Chinetti, G Feugier, P Letexier, D Bricca, G Beylot, M
Citation:	Forcheron F, etal., Arterioscler Thromb Vasc Biol. 2005 Aug;25(8):1711-7. Epub 2005 Jun 16.
RGD ID:	1581042
Pubmed:	PMID:15961705 (View Abstract at PubMed)
DOI:	DOI:10.1161/01.ATV.0000174123.19103.52 (Journal Full-text)
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. CONCLUSIONS: 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.

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
arteriosclerosis		IEP		1581042	mRNA:increased expression:atherosclerotic lesions (human)	RGD
arteriosclerosis		ISO	ACAT1 (Homo sapiens)	1581042; 1581042	mRNA:increased expression:atherosclerotic lesions (human)	RGD

Objects Annotated

Genes (Rattus norvegicus)

Acat1 (acetyl-CoA acetyltransferase 1)

Genes (Mus musculus)

Acat1 (acetyl-Coenzyme A acetyltransferase 1)

Genes (Homo sapiens)

ACAT1 (acetyl-CoA acetyltransferase 1)

Objects referenced in this article

Gene	PLIN1	perilipin 1	Homo sapiens
Gene	Plin1	perilipin 1	Mus musculus
Gene	Plin1	perilipin 1	Rattus norvegicus

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Genes of cholesterol metabolism in human atheroma: overexpression of perilipin and genes promoting cholesterol storage and repression of ABCA1 expression.