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(Circulation. 2009;119:3223-3231.)
© 2009 American Heart Association, Inc.

Molecular Cardiology

ATP-Binding Cassette Transporter A1 Expression and Apolipoprotein A-I Binding Are Impaired in Intima-Type Arterial Smooth Muscle Cells

Hong Y. Choi, PhD; Maziar Rahmani, MD, PhD; Brian W. Wong, BSc; Sima Allahverdian, MD, PhD; Bruce M. McManus, MD, PhD; J. Geoffrey Pickering, MD, PhD; Teddy Chan, MSc; Gordon A. Francis, MD

From the Departments of Medicine (H.Y.C., S.A., T.C., G.A.F.) and Pathology and Laboratory Medicine (M.R., B.W.W., B.M.M.), Heart and Lung Institute, St Paul’s Hospital, Vancouver, British Columbia, Canada, and Vascular Biology Group, Robarts Research Institute, University of Western Ontario, London, Ontario (J.G.P.), Canada. Dr Choi is currently at the Department of Molecular Genetics, UT Southwestern, Dallas, Tex. Dr Rahmani is currently at the Genome Sciences Centre, Vancouver, BC, Canada.

Correspondence to Gordon A. Francis, MD, Room 166, Burrard Bldg, St. Paul’s Hospital, 1081 Burrard St, Vancouver, BC V6Z 1Y6, Canada. E-mail gfrancis{at}mrl.ubc.ca

Received December 4, 2008; accepted May 1, 2009.

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.

Conclusion— 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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CLINICAL PERSPECTIVE

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Clinical Summaries
Circulation 2009 119: 3163-3164. [Extract] [Full Text]