The accumulation of cholesterol in macrophage foam cells results from the uptake of retained and modified apoB lipoproteins (1) and is a central event in atherogenesis.Although it has long been known that HDL and its apolipoproteins can stimulate cholesterol efflux from macrophage foam cells (2, 3) and reduce atherogenesis in animal models (4, 5), this area of research has been enlivened by the elucidation of the genetic defect in Tangier disease, a condition in which there is a defect in apolipoprotein-mediated cholesterol efflux (6) and in which the hallmark pathology is the accumulation of macrophage foam cells in various tissues.Tangier disease is caused by mutations in the ATP-binding cassette transporter A1 (ABCA1).This cell surface transporter facilitates the efflux of phospholipids and cholesterol onto lipid-poor apolipoproteins, initiating the formation of HDL particles.This Perspective will focus on recent studies on the regulation and role of ABCA1 in cellular cholesterol efflux, lipoprotein physiology, and atherogenesis, attempting to place this work in the broader context of studies on cellular cholesterol efflux, centripetal cholesterol transport, and ABC transporter structure and function.
Tall et al. (Tue,) studied this question.