Scavenger receptor BI and ATP-binding cassette transporter A1 in reverse cholesterol transport and atherosclerosis.
OBJECTIVE
The appearance of scavenger receptor class B type I (SR-BI) and ATP-binding cassette transporter A1 (ABCA1) in macrophages and liver implicates these transporters in different stages of reverse cholesterol transport. This review focuses on the role of SR-BI and ABCA1 in reverse cholesterol transport in the context of atherosclerotic lesion development.


RESULTS
Recent studies indicate that hepatic expression of ABCA1 and SR-BI is important for the generation of nascent HDL and the delivery of HDL cholesteryl esters to the liver, respectively. Although macrophage SR-BI and ABCA1 do not contribute significantly to circulating HDL levels, the perpetual cycle of HDL lipidation and delipidation by the liver ensures the availability of acceptors for cholesterol efflux that maintain cholesterol homeostasis in arterial macrophages, thereby reducing atherogenesis. In addition to its established role in the selective uptake of HDL cholesteryl esters, there is now evidence that hepatic SR-BI facilitates postprandial lipid metabolism, and that hepatic secretion of VLDL is dependent on ABCA1-mediated nascent HDL formation. Thus, remnant and HDL metabolism are more intimately intertwined in hepatic lipid metabolism than has previously been appreciated.


CONCLUSIONS
Recent advances in the understanding of the role of ABCA1 and SR-BI in HDL metabolism and their atheroprotective properties indicate the significant potential of modulating ABCA1 and SR-BI expression in both arterial wall macrophages and the liver for the treatment of atherosclerotic coronary artery disease.
Van Eck
Miranda
M
Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Gorlaeus Laboratories, Leiden University, Leiden, The Netherlands. m.eck@lacdr.leidenuniv.nl
Pennings
Marieke
M
Hoekstra
Menno
M
Out
Ruud
R
Van Berkel
Theo Jc
TJ
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000502:physiology*; D001161:Arteriosclerosis / Q000503:physiopathology*; D018955:CD36 Antigens; D002784:Cholesterol / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D008264:Macrophages; D011971:Receptors, Immunologic / Q000502:physiology*; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D018955:CD36 Antigens; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; D002784:Cholesterol