Key result
Intima-type arterial smooth muscle cells show markedly reduced ABCA1 expression and lack cholesterol efflux.
Why the study?
Reduced ABCA1 expression and activity in intimal arterial smooth muscle cells may contribute to foam cell formation in atherosclerotic lesions, but the mechanisms are not fully understood.
Reduced ABCA1 expression and impaired apolipoprotein A-I binding in intimal smooth muscle cells contribute to foam cell formation in atherosclerosis, and cannot be corrected by simply increasing ABCA1 expression.
Impaired ABCA1 in intimal SMCs may promote foam cell formation; leaves open whether efflux-targeted therapies alter human plaque progression.
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. METHODS AND 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.
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Choi et al. (2009) studied Atherosclerosis. Intima-type arterial smooth muscle cells vs. Medial-layer smooth muscle cells was evaluated on ABCA1 expression, apolipoprotein A-I binding, and lipid efflux. Intima-type arterial smooth muscle cells showed markedly diminished ABCA1 expression, poor apoA-I binding, and absence of lipid efflux compared with medial-layer SMCs.
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