Scavenger receptor classes A and B. Their roles in atherogenesis and the metabolism of modified LDL and HDL.
Scavenger-receptor class A has been held responsible for the clearance of modified LDL from the blood circulation. However, in mice deficient in scavenger-receptor class A, the decay in vivo of acetylated LDL (t1/2 < 2 min), as well as tissue distribution and liver uptake (at 5 min 77.4 +/- 4.6% of the injected dose) are not significantly different from control mice. The degradation capacity of acetylated LDL with liver endothelial cells, Kupffer cells, and peritoneal macrophages from knock-out mice was 58%, 63%, and 17% of the control, respectively, indicating that scavenger-receptor class A is relatively more important for the degradation of acetylated LDL and foam cell formation in peritoneal macrophages as compared to the liver cell types. This might explain the 60% reduction in atherosclerotic lesion area in scavenger-receptor-deficient apoE knock-out mice as compared to control apoE knock-out mice. Scavenger-receptor BI can facilitate selective uptake of cholesterol esters from HDL. A high cholesterol diet for two weeks induced an 80% downregulation of scavenger-receptor BI in the liver parenchymal cells while expression in liver macrophages is increased fourfold. The in vivo kinetics for the selective uptake of (oxidized) cholesterol esters from HDL correlate with the changes in scavenger-receptor BI expression. It is suggested that scavenger-receptor BI is subject to different regulatory mechanisms in parenchymal liver cells and macrophages related to a difference in function in these cell types.
Van Berkel
T J
TJ
Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, University of Leiden, The Netherlands.
Van Eck
M
M
Herijgers
N
N
Fluiter
K
K
Nion
S
S
D000818:Animals; D001161:Arteriosclerosis / Q000503:physiopathology*; D018955:CD36 Antigens / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000502:physiology; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D011971:Receptors, Immunologic / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D018110:Receptors, Lipoprotein / Q000502:physiology; D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A; D051122:Scavenger Receptors, Class B
D018955:CD36 Antigens; D015815:Cell Adhesion Molecules; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; C495139:MSR1 protein, human; D008565:Membrane Proteins; C495140:Msr1 protein, mouse; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051117:Scavenger Receptors, Class A; D051122:Scavenger Receptors, Class B