Linked Life Data

8148358

Source:http://linkedlifedata.com/resource/pubmed/id/8148358

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1994-5-12
pubmed:abstractText
Rabbits fed low-fat, cholesterol-free diets containing casein as the sole protein source develop endogenous hypercholesterolemia (EH). To test the hypothesis that lipoprotein cholesteryl esters in EH rabbits are acyl coenzyme A:cholesterol acyltransferase (ACAT) derived, we treated EH rabbits with CI-976, a potent and selective ACAT inhibitor. In addition, since cholesterol and bile acid synthesis as well as low-density lipoprotein (LDL) receptor activity are reduced in EH rabbits, we determined whether changes in gene expression for 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, 7 alpha-hydroxylase, and the LDL receptor might be associated with the efficacy due to ACAT inhibition. Compared with EH controls, CI-976-treated rabbits (50 mg/kg per day for 5 weeks) had decreased plasma total cholesterol (-43%), very-low-density lipoprotein (VLDL) cholesterol (-62%), LDL cholesterol (-43%), plasma apolipoprotein B (-23%), liver cholesteryl esters (-39%), LDL size, VLDL and LDL cholesteryl ester content (percent of total lipids), cholesteryl oleate/cholesteryl linoleate ratios in VLDL and LDL (25% to 30%), and ex vivo liver ACAT activity. The triglyceride/cholesteryl ester ratio increased twofold to fourfold in these apolipoprotein B-containing lipoproteins. Endogenous cholesterol absorption appeared to be unaffected by drug treatment. CI-976 failed to alter specific hepatic mRNAs involved in cholesterol metabolism, but comparisons among dietary control groups revealed a marked reduction in 7 alpha-hydroxylase mRNA, no change in LDL receptor mRNA, and an increase in HMG-CoA reductase mRNA in EH rabbits compared with normal chow-fed controls.(ABSTRACT TRUNCATED AT 250 WORDS)
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Anilides, http://linkedlifedata.com/resource/pubmed/chemical/Aryl Hydrocarbon Hydroxylases, http://linkedlifedata.com/resource/pubmed/chemical/Cholesterol, http://linkedlifedata.com/resource/pubmed/chemical/Cholesterol, LDL, http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome P-450 Enzyme System, http://linkedlifedata.com/resource/pubmed/chemical/Dietary Fats, http://linkedlifedata.com/resource/pubmed/chemical/Hydroxymethylglutaryl CoA Reductases, http://linkedlifedata.com/resource/pubmed/chemical/PD 128042, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, LDL, http://linkedlifedata.com/resource/pubmed/chemical/Steroid Hydroxylases, http://linkedlifedata.com/resource/pubmed/chemical/Sterol O-Acyltransferase, http://linkedlifedata.com/resource/pubmed/chemical/steroid hormone 7-alpha-hydroxylase
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1049-8834
pubmed:author
pubmed:issnType
Print
pubmed:volume
14
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
598-604
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
ACAT inhibition decreases LDL cholesterol in rabbits fed a cholesterol-free diet. Marked changes in LDL cholesterol without changes in LDL receptor mRNA abundance.
pubmed:affiliation
Department of Atherosclerosis Therapeutics, Parke-Davis Research Division of Warner Lambert Co, Ann Arbor, MI 48105.
pubmed:publicationType
Journal Article