Source:http://linkedlifedata.com/resource/pubmed/id/10393217
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
7
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pubmed:dateCreated |
1999-8-4
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pubmed:abstractText |
An orally bioavailable acyl coenzyme A:cholesterol acyltransferase (ACAT) inhibitor, avasimibe (CI-1011), was used to test the hypothesis that inhibition of cholesterol esterification, in vivo, would reduce hepatic very low density (VLDL) apolipoprotein (apo) B secretion into plasma. ApoB kinetic studies were carried out in 10 control miniature pigs, and in 10 animals treated with avasimibe (10 mg/kg/d, n = 6; 25 mg/kg/d, n = 4). Pigs were fed a diet containing fat (34% of calories) and cholesterol (400 mg/d; 0.1%). Avasimibe decreased the plasma concentrations of total triglyceride, VLDL triglyceride, and VLDL cholesterol by 31;-40% 39-48%, and 31;-35%, respectively. Significant reductions in plasma total cholesterol (35%) and low density lipoprotein (LDL) cholesterol (51%) concentrations were observed only with high dose avasimibe. Autologous 131I-labeled VLDL, 125I-labeled LDL, and [3H]leucine were injected simultaneously into each pig and apoB kinetic data were analyzed using multicompartmental analysis (SAAM II). Avasimibe decreased the VLDL apoB pool size by 40;-43% and the hepatic secretion rate of VLDL apoB by 38;-41%, but did not alter its fractional catabolism. Avasimibe decreased the LDL apoB pool size by 13;-57%, largely due to a dose-dependent 25;-63% in the LDL apoB production rate. Hepatic LDL receptor mRNA abundances were unchanged, consistent with a marginal decrease in LDL apoB FCRs. Hepatic ACAT activity was decreased by 51% (P = 0.050) and 68% (P = 0.087) by low and high dose avasimibe, respectively. The decrease in total apoB secretion correlated with the decrease in hepatic ACAT activity (r = 0.495; P = 0.026). We conclude that inhibition of hepatic ACAT by avasimibe reduces both plasma VLDL and LDL apoB concentrations, primarily by decreasing apoB secretion.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Acetates,
http://linkedlifedata.com/resource/pubmed/chemical/Anticholesteremic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Apolipoproteins B,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Lipoproteins, LDL,
http://linkedlifedata.com/resource/pubmed/chemical/Lipoproteins, VLDL,
http://linkedlifedata.com/resource/pubmed/chemical/Sterol O-Acyltransferase,
http://linkedlifedata.com/resource/pubmed/chemical/Sulfonic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/avasimibe
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0022-2275
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
40
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1317-27
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pubmed:dateRevised |
2009-11-3
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pubmed:meshHeading |
pubmed-meshheading:10393217-Acetates,
pubmed-meshheading:10393217-Animals,
pubmed-meshheading:10393217-Anticholesteremic Agents,
pubmed-meshheading:10393217-Apolipoproteins B,
pubmed-meshheading:10393217-Enzyme Inhibitors,
pubmed-meshheading:10393217-Female,
pubmed-meshheading:10393217-Lipoproteins, LDL,
pubmed-meshheading:10393217-Lipoproteins, VLDL,
pubmed-meshheading:10393217-Liver,
pubmed-meshheading:10393217-Male,
pubmed-meshheading:10393217-Sterol O-Acyltransferase,
pubmed-meshheading:10393217-Sulfonic Acids,
pubmed-meshheading:10393217-Swine,
pubmed-meshheading:10393217-Swine, Miniature
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pubmed:year |
1999
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pubmed:articleTitle |
Inhibition of ACAT by avasimibe decreases both VLDL and LDL apolipoprotein B production in miniature pigs.
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pubmed:affiliation |
Departments of Medicine and Biochemistry and The John P. Robarts Research Institute, University of Western Ontario, London, Ontario N6A 5K8, Canada.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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