| The effect of 17β-estradiol on cholesterol content in human macrophages is influenced by the lipoprotein milieu. | |
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MedLine Citation:
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PMID: 21830321 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Estrogen and testosterone are thought to modulate coronary heart disease (CHD) risk. To examine how these hormones affect human macrophage cholesterol transport, a key factor in atherogenesis, we obtained monocytes from healthy male and postmenopausal female donors (age 50–70 years). Cells were allowed to differentiate in autologous serum. Human monocyte-derived macrophages (HMDMs) were exposed to estrogen, testosterone, or vehicle, during differentiation.Cells were cholesterol enriched with oxidized low-density lipoprotein (oxLDL) in the presence of treatment. Cell cholesterol mass, efflux, and the expression of proteins involved in HMDM cholesterol transport were examined.Estrogen significantly reduced cholesteryl ester (CE) content in both female and male HMDMs while having no measurable effect on cholesterol efflux. Testosterone did not affect cholesterol content or efflux. Both hormones significantly but modestly affected the gene expression of several proteins involved in HMDM transport, yet these effects did not translate into significant changes in protein expression. In THP-1 macrophages, the effect of estrogen on CE content was more potent in unloaded macrophages and was estrogen receptor dependent. A trend for a reduction in nonoxLDL uptake by estrogen was observed and was also found to be dependent upon estrogen receptor activation. Our data indicate that estrogen, but not testosterone, reduces CE accumulation in HMDMs obtained from a CHD age relevant population, independent of changes in the expression of proteins important to macrophage cholesterol transport. In THP-1 cells, this effect is reduced in the presence of oxLDL, indicating that a pro-atherogenic lipoprotein milieu is an important variable in sex hormone modulation of CHD. |
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Authors:
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Michael P Corcoran; Alice H Lichtenstein; Mohsen Meydani; Alice Dillard; Ernst J Schaefer; Stefania Lamon-Fava |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of molecular endocrinology Volume: 47 ISSN: 1479-6813 ISO Abbreviation: J. Mol. Endocrinol. Publication Date: 2011 Aug |
Date Detail:
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Created Date: 2011-08-08 Completed Date: 2011-10-17 Revised Date: 2012-03-02 |
Medline Journal Info:
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Nlm Unique ID: 8902617 Medline TA: J Mol Endocrinol Country: England |
Other Details:
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Languages: eng Pagination: 109-117 Citation Subset: IM |
Affiliation:
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Lipid Metabolism Laboratory, Tufts University, Boston, Massachusetts 02111, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Aged Cells, Cultured Cholesterol / metabolism* Cholesterol Esters / metabolism Cholesterol, HDL / blood Cholesterol, LDL / blood Estradiol / pharmacology* Female Gene Expression Profiling Humans Lipoproteins / metabolism* Lipoproteins, LDL / pharmacology Macrophages / drug effects, metabolism* Male Middle Aged Postmenopause / blood Testosterone / pharmacology Transcription, Genetic / drug effects Triglycerides / blood |
| Grant Support | |
ID/Acronym/Agency:
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T32 HL069772-01A1/HL/NHLBI NIH HHS; T32 HL69772-01A1/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cholesterol Esters; 0/Cholesterol, HDL; 0/Cholesterol, LDL; 0/Lipoproteins; 0/Lipoproteins, LDL; 0/Triglycerides; 0/oxidized low density lipoprotein; 50-28-2/Estradiol; 57-88-5/Cholesterol; 58-22-0/Testosterone |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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