Plasma levels of 27-hydroxycholesterol in humans and mice with monogenic disturbances of high density lipoprotein metabolism
- PMID: 21130455
- DOI: 10.1016/j.atherosclerosis.2010.10.042
Plasma levels of 27-hydroxycholesterol in humans and mice with monogenic disturbances of high density lipoprotein metabolism
Abstract
Secretion of 27-hydroxycholesterol (27OHC) from macrophages is considered as an alternative to HDL-mediated reverse transport of excess cholesterol. We investigated 27OHC-concentrations in plasma of humans and mice with monogenic disorders of HDL metabolism. As compared to family controls mutations in the genes for apolipoprotein A-I, ATP binding cassette transporter (ABC) A1 and lecithin:cholesterol acylstransferase (LCAT) were associated with reduced concentrations of both HDL-cholesterol and HDL-27OHC whereas mutations in the genes for cholesterylester transfer protein (CETP), scavenger receptor type BI and hepatic lipase were associated with elevated HDL concentrations of either sterol. Compared to family controls and relative to the concentrations of total 27OHC and cholesterol, lower 27OHC-ester but normal cholesterylester levels were found in HDL of heterozygous LCAT mutation carriers and nonHDL of heterozygous CETP mutation carriers. In family controls, LCAT activity and CETP mass were more strongly correlated with 27OHC-ester than cholesterylester concentrations in HDL and nonHDL, respectively. These findings suggest that the formation and transfer of 27OHC-esters are more sensitive to reduced activities of LCAT and CETP, respectively, than the formation and transfer of cholesterylesters. 27OHC plasma levels were also decreased in apoA-I-, ABCA1- or LCAT-knockout mice but increased in SR-BI-knockout mice. Transplantation of ABCA1- and/or ABCG1-deficient bone marrow into LDL receptor deficient mice decreased plasma levels of 27OHC. In conclusion, mutations or absence of HDL genes lead to distinct alterations in the quantity, esterification or lipoprotein distribution of 27OHC. These findings argue against the earlier suggestion that 27OHC-metabolism in plasma occurs independently of HDL.
Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.
Similar articles
-
Mouse models of disturbed HDL metabolism.Handb Exp Pharmacol. 2015;224:301-36. doi: 10.1007/978-3-319-09665-0_9. Handb Exp Pharmacol. 2015. PMID: 25522993 Review.
-
Lipoprotein distribution and serum concentrations of 7α-hydroxy-4-cholesten-3-one and bile acids: effects of monogenic disturbances in high-density lipoprotein metabolism.Clin Sci (Lond). 2012 Apr;122(8):385-96. doi: 10.1042/CS20110482. Clin Sci (Lond). 2012. PMID: 22010943
-
Plasma levels of sphingosine-1-phosphate and apolipoprotein M in patients with monogenic disorders of HDL metabolism.Atherosclerosis. 2011 Dec;219(2):855-63. doi: 10.1016/j.atherosclerosis.2011.08.049. Epub 2011 Sep 6. Atherosclerosis. 2011. PMID: 21944699
-
Adipocyte modulation of high-density lipoprotein cholesterol.Circulation. 2010 Mar 23;121(11):1347-55. doi: 10.1161/CIRCULATIONAHA.109.897330. Epub 2010 Mar 8. Circulation. 2010. PMID: 20212278 Free PMC article.
-
Role of apoA-I, ABCA1, LCAT, and SR-BI in the biogenesis of HDL.J Mol Med (Berl). 2006 Apr;84(4):276-94. doi: 10.1007/s00109-005-0030-4. Epub 2006 Feb 25. J Mol Med (Berl). 2006. PMID: 16501936 Review.
Cited by
-
Hepatocyte ABCA1 deficiency is associated with reduced HDL sphingolipids.Front Physiol. 2023 Aug 4;14:1208719. doi: 10.3389/fphys.2023.1208719. eCollection 2023. Front Physiol. 2023. PMID: 37601634 Free PMC article.
-
Role of reactive oxygen species in regulating 27-hydroxycholesterol-induced apoptosis of hematopoietic progenitor cells and myeloid cell lines.Cell Death Dis. 2022 Oct 31;13(10):916. doi: 10.1038/s41419-022-05360-0. Cell Death Dis. 2022. PMID: 36316327 Free PMC article.
-
Metabolic reprograming of MDSCs within tumor microenvironment and targeting for cancer immunotherapy.Acta Pharmacol Sin. 2022 Jun;43(6):1337-1348. doi: 10.1038/s41401-021-00776-4. Epub 2021 Sep 24. Acta Pharmacol Sin. 2022. PMID: 34561553 Free PMC article. Review.
-
Dysregulated cholesterol homeostasis results in resistance to ferroptosis increasing tumorigenicity and metastasis in cancer.Nat Commun. 2021 Aug 24;12(1):5103. doi: 10.1038/s41467-021-25354-4. Nat Commun. 2021. PMID: 34429409 Free PMC article.
-
The Cholesterol Metabolite 27HC Increases Secretion of Extracellular Vesicles Which Promote Breast Cancer Progression.Endocrinology. 2021 Jul 1;162(7):bqab095. doi: 10.1210/endocr/bqab095. Endocrinology. 2021. PMID: 33959755 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Research Materials
Miscellaneous