Oxidized or acetylated low density lipoproteins are rapidly cleared by the liver in mice with disruption of the scavenger receptor class A type I/II gene
- PMID: 9218499
- PMCID: PMC508185
- DOI: 10.1172/JCI119528
Oxidized or acetylated low density lipoproteins are rapidly cleared by the liver in mice with disruption of the scavenger receptor class A type I/II gene
Abstract
Oxidized low density lipoprotein (LDL) and acetyl LDL are recognized by the scavenger receptor class A type I/II (SR-AI/II) on macrophages and liver endothelial cells. Several investigators have suggested that there are additional receptors specific for oxidized LDL, but characterization of these alternate receptors for oxidized LDL and evaluation of their quantitative importance in uptake of oxidized LDL has been difficult because of overlapping ligand specificity with SR-AI/II. The purpose of this study was to determine the importance of SR-AI/II in the removal of modified LDL from the bloodstream in vivo. The clearance rate of oxidized LDL from plasma in normal mice was very rapid, and > 90% of injected dose was removed from the blood within 5 min. Clearance rates of oxidized LDL were equally high in SR-AI/II knockout mice, indicating that this receptor is not required for removal of oxidized LDL from plasma. Surprisingly, there was no difference in the clearance rate of acetyl LDL in wild-type and SR-AI/II knockout animals. The plasma clearance of radioiodinated acetyl LDL was almost fully blocked by a 50-fold excess of unlabeled acetyl LDL, but the latter only inhibited oxidized LDL clearance by approximately 5%. Both modified LDLs were cleared mostly by the liver, and there was no difference in the tissue distribution of modified LDL in control and knockout mice. Studies in isolated nonparenchymal liver cells showed that Kupffer cells accounted for most of the uptake of oxidized LDL. Extensively oxidized LDL and LDL modified by exposure to fatty acid peroxidation products were efficient competitors for the uptake of labeled oxidized LDL by SR-AI/II-deficient Kupffer cells, while acetyl LDL and malondialdehyde-modified LDL were relatively poor competitors.
Similar articles
-
High affinity saturable uptake of oxidized low density lipoprotein by macrophages from mice lacking the scavenger receptor class A type I/II.J Biol Chem. 1997 May 16;272(20):12938-44. doi: 10.1074/jbc.272.20.12938. J Biol Chem. 1997. PMID: 9148899
-
The role of human and mouse hepatic scavenger receptor class B type I (SR-BI) in the selective uptake of low-density lipoprotein-cholesteryl esters.Biochemistry. 2003 Jun 24;42(24):7527-38. doi: 10.1021/bi026949a. Biochemistry. 2003. PMID: 12809509
-
Low-density lipoprotein from apolipoprotein E-deficient mice induces macrophage lipid accumulation in a CD36 and scavenger receptor class A-dependent manner.Arterioscler Thromb Vasc Biol. 2005 Jan;25(1):168-73. doi: 10.1161/01.ATV.0000149145.00865.d9. Epub 2004 Oct 28. Arterioscler Thromb Vasc Biol. 2005. PMID: 15514202
-
Scavenger receptors for oxidized and glycated proteins.Amino Acids. 2003 Dec;25(3-4):283-92. doi: 10.1007/s00726-003-0029-5. Epub 2003 Aug 21. Amino Acids. 2003. PMID: 14661091 Review.
-
Scavenger receptors and modified lipoproteins: fatal attractions?IUBMB Life. 2000 May;49(5):397-403. doi: 10.1080/152165400410245. IUBMB Life. 2000. PMID: 10902571 Review.
Cited by
-
PPARgamma regulates adipocyte cholesterol metabolism via oxidized LDL receptor 1.J Clin Invest. 2005 Aug;115(8):2244-56. doi: 10.1172/JCI24130. Epub 2005 Jul 7. J Clin Invest. 2005. PMID: 16007265 Free PMC article.
-
Role of liver sinusoidal endothelial cells and stabilins in elimination of oxidized low-density lipoproteins.Am J Physiol Gastrointest Liver Physiol. 2011 Jan;300(1):G71-81. doi: 10.1152/ajpgi.00215.2010. Epub 2010 Oct 28. Am J Physiol Gastrointest Liver Physiol. 2011. PMID: 21030611 Free PMC article.
-
Prominent Receptors of Liver Sinusoidal Endothelial Cells in Liver Homeostasis and Disease.Front Physiol. 2020 Jul 21;11:873. doi: 10.3389/fphys.2020.00873. eCollection 2020. Front Physiol. 2020. PMID: 32848838 Free PMC article. Review.
-
Rapamycin Inhibits Oxidized Low Density Lipoprotein Uptake in Human Umbilical Vein Endothelial Cells via mTOR/NF-κB/LOX-1 Pathway.PLoS One. 2016 Jan 11;11(1):e0146777. doi: 10.1371/journal.pone.0146777. eCollection 2016. PLoS One. 2016. PMID: 26752047 Free PMC article.
-
Antagonism of RNase L Is Required for Murine Coronavirus Replication in Kupffer Cells and Liver Sinusoidal Endothelial Cells but Not in Hepatocytes.J Virol. 2016 Oct 14;90(21):9826-9832. doi: 10.1128/JVI.01423-16. Print 2016 Nov 1. J Virol. 2016. PMID: 27558415 Free PMC article.
References
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Molecular Biology Databases
Research Materials