Significance of ABCA1 in human carotid atherosclerotic plaques

Abstract

The ATP-binding cassette transporter A1 (ABCA1) is an important effector in the regulation of cholesterol efflux from cells. In this study, we assessed the role of ABCA1 in human carotid atherosclerotic plaques (CAPs). We found that ABCA1 and retinoid X receptor α (RXRα) mRNAs were significantly increased in the atherosclerotic plaques compared to control arteries. The increased ABCA1 mRNA correlated with that of RXRα in plaques. According to the modified American Heart Association plaque classification, atherosclerotic specimens were assigned to three grades, and ABCA1 and RXRα mRNA levels were compared across plaques of different grades. Resultantly, plaques of grade II and III exhibited higher mRNA levels than grade I, but there was no difference in mRNA levels between plaques of grade II and III. By contrast, ABCA1 and RXRα protein levels were notably reduced in plaques relative to control tissues. Similarly, plaques of grade II and III exhibited lower ABCA1 and RXRα protein levels than grade I, and there was no difference in protein levels between plaques of grade II and III. Our findings suggest that decreased ABCA1 protein plays a key role in the pathogenesis of CAP; the regulation of ABCA1 may be mediated by RXRα and ABCA1 mRNA levels may serve as an indicator for plaque stability.