Published Online
on November 4, 2004

A more recent version of this article appeared on December 1, 2004

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Submitted on January 15, 2004
Revised on July 30, 2004
Accepted on August 24, 2004

ABCA1 Expression in Carotid Atherosclerotic Plaques

C. Albrecht PhD; S. Soumian FRCS; J. S. Amey MSc; A. Sardini PhD; C. F. Higgins PhD; A. H. Davies FRCS; and R. G.J. Gibbs FRCS^*

From the MRC Clinical Sciences Centre (C.A., J.S.A., A.S., C.F.H.), Faculty of Medicine, Imperial College, Hammersmith Hospital, Du Cane Road, London, UK; the Department of Vascular Surgery (S.S., A.H.D., R.G.J.G.), Faculty of Medicine, Imperial College, Charing Cross Hospital, Fulham Palace Road, London, UK. Current affiliation for C.A. is Physiology Weihenstephan, Technical University Munich, Weihenstephaner Berg 3, Freising, Germany.

^* To whom correspondence should be addressed. E-mail: r.gibbs{at}ic.ac.uk.

Background and Purpose--The ATP-binding cassette transporter A1 (ABCA1) facilitates cholesterol efflux from cells, a key process in reverse cholesterol transport. Whereas previous investigations focused on mutations causing impaired ABCA1 function, we assessed the role of ABCA1 in human carotid atherosclerotic disease.

Methods--We compared the mRNA and protein levels of ABCA1, and one of its key regulators, the liver X receptor (LXR), between minimally and grossly atherosclerotic arterial tissue. We established ABCA1 and LXR gene expression by real-time quantitative polymerase chain reaction in 10 control and 18 atherosclerotic specimens. Presence of ABCA1 protein was assessed by immunoblotting. To determine whether differences observed at a local level were reflected in the systemic circulation, we measured ABCA1 mRNA in leukocytes of 10 patients undergoing carotid endarterectomy and 10 controls without phenotypic atherosclerosis.

Results--ABCA1 and LXR gene expression were significantly elevated in atherosclerotic plaques (P<0.0001 and 0.03, respectively). The increased mRNA levels of ABCA1 and LXR were correlated in atherosclerotic tissue (r=0.85; P<0.0001). ABCA1 protein expression was significantly reduced in plaques compared with control tissues (P<0.0001). There were no differences in leukocyte ABCA1 mRNA expression (P=0.67).

Conclusions--ABCA1 gene and protein are expressed in minimally atherosclerotic human arteries. Despite significant upregulation of ABCA1 mRNA, possibly mediated via LXR, ABCA1 protein is markedly reduced in advanced carotid atherosclerotic lesions. No differences in leukocyte ABCA1 expression were found, suggesting the plaque microenvironment may contribute to the differential ABCA1 expression. We propose that the decreased level of ABCA1 protein is a key factor in the development of atherosclerotic lesions.

Key words: atherosclerosis • ATP binding cassette transporter 1 • carotid artery plaque • carotid arteries • polymerase chain reaction

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