Relative roles of various efflux pathways in net cholesterol efflux from macrophage foam cells in atherosclerotic lesions.
OBJECTIVE
Cholesterol efflux mechanisms are essential for macrophage cholesterol homeostasis. HDL, an important cholesterol efflux acceptor, comprises a class of heterogeneous particles that induce cholesterol efflux via distinct pathways. This review focuses on the understanding of the different cholesterol efflux pathways and physiological acceptors involved, and their regulation in atherosclerotic lesions.


RESULTS
The synergistic interactions of ATP-binding cassette transporters A1 and G1 as well as ATP-binding cassette transporter A1 and scavenger receptor class B type I are essential for cellular cholesterol efflux and the prevention of macrophage foam cell formation. However, the importance of aqueous diffusion should also not be underestimated. Significant progress has been made in understanding the mechanisms underlying ATP-binding cassette A1-mediated cholesterol efflux and regulation of its expression and trafficking. Conditions locally in the atherosclerotic lesion, for example, lipids, cytokines, oxidative stress, and hypoxia, as well as systemic factors, including inflammation and diabetes, critically influence the expression of cholesterol transporters on macrophage foam cells. Furthermore, HDL modification and remodeling in atherosclerosis, inflammation, and diabetes impairs its function as an acceptor for cellular cholesterol.


CONCLUSIONS
Recent advances in the understanding of the regulation of cholesterol transporters and their acceptors in atherosclerotic lesions indicate that HDL-based therapies should aim to enhance the activity of cholesterol transporters and improve both the quantity and quality of HDL.
Zhao
Ying
Y
Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, University of Leiden, Leiden, The Netherlands.
Van Berkel
Theo Jc
TJ
Van Eck
Miranda
M
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D002784:Cholesterol / Q000378:metabolism*; D005487:Foam Cells / Q000378:metabolism*; D006801:Humans; D058226:Plaque, Atherosclerotic / Q000378:metabolism* / Q000473:pathology*; D051116:Receptors, Scavenger / Q000378:metabolism
D018528:ATP-Binding Cassette Transporters; D051116:Receptors, Scavenger; D002784:Cholesterol