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


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.
Forcheron
Fabien
F
INSERM U499, Faculté Laennec, UCB Lyon I, Lyon, France.
Legedz
Liliana
L
Chinetti
Guiletta
G
Feugier
Patrick
P
Letexier
Dominique
D
Bricca
Giampierro
G
Beylot
Michel
M
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism; D000368:Aged; D000818:Animals; D001158:Arteries / Q000378:metabolism / Q000473:pathology; D050197:Atherosclerosis / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D018955:CD36 Antigens / Q000235:genetics; D002352:Carrier Proteins; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D005260:Female; D005487:Foam Cells / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology; D000070778:Perilipin-1; D000070780:Perilipin-2; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011924:Rats, Zucker; D002785:Sterol O-Acyltransferase / Q000235:genetics
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D018955:CD36 Antigens; D002352:Carrier Proteins; D008565:Membrane Proteins; C000602982:PLIN2 protein, human; D000070778:Perilipin-1; D000070780:Perilipin-2; D010750:Phosphoproteins; C000602984:Plin2 protein, rat; D012333:RNA, Messenger; D002784:Cholesterol; D002785:Sterol O-Acyltransferase; C493492:sterol O-acyltransferase 1