| Estrogen decreases atherosclerosis in part by reducing hepatic acyl-CoA:cholesterol acyltransferase 2 (ACAT2) in monkeys. | |
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MedLine Citation:
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PMID: 19759374 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: Estrogens decrease atherosclerosis progression, mediated in part through changes in plasma lipids and lipoproteins. This study aimed to determine estrogen-induced changes in hepatic cholesterol metabolism, plasma lipoproteins, and the relationship of these changes to atherosclerosis extent. METHODS AND RESULTS: Ovariectomized monkeys (n=34) consumed atherogenic diets for 30 months which contained either no hormones (control, n=17) or conjugated equine estrogens (CEE, n=17) at a human dose equivalent of 0.625 mg/d. Hepatic cholesterol content, low-density lipoprotein (LDL) receptor expression, cholesterol 7 alpha-hydroxylase and acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity, and expression levels were determined. CEE treatment resulted in lower plasma concentrations of very-low- and intermediate- density lipoprotein cholesterol (V+IDLC; P=0.01), smaller LDL particles (P=0.002), and 50% lower hepatic cholesterol content (total, free, and esterified; P<0.05 for all). Total ACAT activity was significantly lower (P=0.01), explained primarily by reductions in the activity of ACAT2. Estrogen regulation of enzymatic activity was at the protein level as both ACAT1 and 2 protein, but not mRNA levels, were lower (P=0.02 and <0.0001, respectively). ACAT2 activity was significantly associated with hepatic total cholesterol, plasma V+IDLC cholesterol, and atherosclerosis. CONCLUSIONS: Atheroprotective effects of estrogen therapy may be related to reduced hepatic secretion of ACAT2-derived cholesteryl esters in plasma lipoproteins. |
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Authors:
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Kylie Kavanagh; Matthew A Davis; Li Zhang; Martha D Wilson; Thomas C Register; Michael R Adams; Lawrence L Rudel; Janice D Wagner |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Arteriosclerosis, thrombosis, and vascular biology Volume: 29 ISSN: 1524-4636 ISO Abbreviation: Arterioscler. Thromb. Vasc. Biol. Publication Date: 2009 Oct |
Date Detail:
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Created Date: 2009-09-17 Completed Date: 2009-09-29 Revised Date: 2010-12-03 |
Medline Journal Info:
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Nlm Unique ID: 9505803 Medline TA: Arterioscler Thromb Vasc Biol Country: United States |
Other Details:
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Languages: eng Pagination: 1471-7 Citation Subset: IM |
Affiliation:
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Department of Pathology, Section on Comparative Medicine, Wake Forest University School of Medicine, Medical Center Blvd, Winston-Salem, NC 27157, USA. kkavanag@wfubmc.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Atherosclerosis / prevention & control* Estrogens, Conjugated (USP) / pharmacology* Female Lipoproteins, LDL / blood Liver / enzymology* Macaca fascicularis Sterol O-Acyltransferase / antagonists & inhibitors* Triglycerides / blood |
| Grant Support | |
ID/Acronym/Agency:
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5 T32 HL07115/HL/NHLBI NIH HHS; HL-49373/HL/NHLBI NIH HHS; HL-P01-45666/HL/NHLBI NIH HHS; P01 HL045666-089002/HL/NHLBI NIH HHS; P01 HL049373-179001/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Estrogens, Conjugated (USP); 0/Lipoproteins, LDL; 0/Triglycerides; EC 2.3.1.26/Sterol O-Acyltransferase; EC 2.3.1.26/sterol O-acyltransferase 2 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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