ATP-binding cassette transporter A1 expression and apolipoprotein A-I binding are impaired in intima-type arterial smooth muscle cells.
BACKGROUND
Accumulation of excess cholesterol by intimal arterial smooth muscle cells (SMCs) contributes to the formation of foam cells in atherosclerotic lesions. The purpose of this study was to examine the expression and activity of ATP-binding cassette transporter A1 (ABCA1) in model intimal and medial arterial SMCs, in human atherosclerotic coronary artery intimal and medial layers, and in human intimal and medial SMCs.


RESULTS
Model intimal arterial SMCs showed increased cholesteryl ester accumulation, absence of apolipoprotein A-I-mediated lipid efflux, markedly diminished ABCA1 expression, and poor apoA-I binding compared with medial-layer SMCs. Total ABCA1 mRNA and SMC-specific ABCA1 protein levels were diminished in the intimal layer compared with the medial layer of atherosclerotic human coronary arteries. Increased expression of ABCA1 by liver X receptor agonist treatment or gene transfection failed to correct apolipoprotein A-I binding, lipid efflux, or high-density lipoprotein particle formation by intima-type SMCs. In addition to impaired ABCA1 expression, intima-type SMCs appear to lack a critical binding factor or factors required for the apolipoprotein A-I-ABCA1 interaction, cholesterol efflux, and high-density lipoprotein particle formation.


CONCLUSIONS
ABCA1 expression is reduced in cultured model intimal and human atherosclerotic lesion SMCs, suggesting that reduced ABCA1 activity contributes to smooth muscle foam cell formation in the intima.
Choi
Hong Y
HY
Department of Medicine, Heart and Lung Institute, St. Paul's Hospital, 1081 Burrard Street, Vancouver, BC, Canada.
Rahmani
Maziar
M
Wong
Brian W
BW
Allahverdian
Sima
S
McManus
Bruce M
BM
Pickering
J Geoffrey
JG
Chan
Teddy
T
Francis
Gordon A
GA
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology; D016632:Apolipoprotein A-I / Q000378:metabolism* / Q000494:pharmacology; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D003324:Coronary Artery Disease / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D003331:Coronary Vessels / Q000473:pathology; D005487:Foam Cells / Q000473:pathology; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D016632:Apolipoprotein A-I; D008075:Lipoproteins, HDL; D012333:RNA, Messenger; D002784:Cholesterol