Regulation of cholesterol homeostasis in macrophages and consequences for atherosclerotic lesion development.
Foam cell formation due to excessive accumulation of cholesterol by macrophages is a pathological hallmark of atherosclerosis. Macrophages cannot limit the uptake of cholesterol and therefore depend on cholesterol efflux pathways for preventing their transformation into foam cells. Several ABC-transporters, including ABCA1 and ABCG1, facilitate the efflux of cholesterol from macrophages. These transporters, however, also affect membrane lipid asymmetry which may have important implications for cellular endocytotic pathways. We propose that in addition to the generally accepted role of these ABC-transporters in the prevention of foam cell formation by induction of cholesterol efflux from macrophages, they also influence the macrophage endocytotic uptake.
Pennings
Marieke
M
Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Gorlaeus Laboratories, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands.
Meurs
Illiana
I
Ye
Dan
D
Out
Ruud
R
Hoekstra
Menno
M
Van Berkel
Theo J C
TJ
Van Eck
Miranda
M
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology*; D002462:Cell Membrane / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D008264:Macrophages / Q000378:metabolism*
D018528:ATP-Binding Cassette Transporters; D002784:Cholesterol