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rdf:type |
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lifeskim:mentions |
umls-concept:C0008377,
umls-concept:C0018557,
umls-concept:C0023824,
umls-concept:C0032105,
umls-concept:C0079429,
umls-concept:C0205054,
umls-concept:C0243102,
umls-concept:C0348011,
umls-concept:C0392756,
umls-concept:C0439810,
umls-concept:C0442805,
umls-concept:C0599930,
umls-concept:C0679058,
umls-concept:C1547699,
umls-concept:C1705822,
umls-concept:C2700640
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pubmed:issue |
2
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pubmed:dateCreated |
1995-9-11
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pubmed:abstractText |
Clinical interventions that accelerate conversion of cholesterol to bile acids reduce circulating low density lipoprotein (LDL) cholesterol concentrations. The initial and rate-limiting step in the bile acid biosynthetic pathway is catalyzed by hepatic cholesterol 7 alpha-hydroxylase. To examine the effects of transient primary overexpression of this enzyme on sterol metabolism and lipoprotein transport, we constructed a recombinant adenovirus in which a cDNA encoding rat 7 alpha-hydroxylase is expressed from the human cytomegalovirus immediate-early promoter (AdCMV7 alpha). Syrian hamsters administered AdCMV7 alpha intravenously accumulated transgene-specific mRNA in the liver and demonstrated a dose-dependent increase in hepatic microsomal 7 alpha-hydroxylase activity. The increased conversion of cholesterol to bile acids resulted in a compensatory increase in hepatic cholesterol synthesis. In addition, overexpression of 7 alpha-hydroxylase reduced the rate of LDL cholesterol entry into the plasma space and, in animals maintained on a Western-type diet, restored hepatic LDL receptor expression. As a consequence, plasma LDL concentrations fell by approximately 60% in animals maintained on control diet and by approximately 75% in animals consuming a Western-type diet. Plasma high density lipoprotein cholesterol levels were reduced to a lesser degree. These results demonstrate that transient upregulation of bile acid synthesis by direct transfer of a 7 alpha-hydroxylase gene favorably alters circulating lipoprotein profiles and suggest one potential molecular target for genetic strategies aimed at reducing cardiovascular risk.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/7635963-1334082,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7635963-1374564,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7635963-1429619,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7635963-1544932,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7635963-1591235,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7635963-1693613,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7635963-1784233,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7635963-1793446,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7635963-1943733,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7635963-1967820,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7635963-1995604,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7635963-2044648,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7635963-2090716,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7635963-2205799,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7635963-2440339,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7635963-2448340,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7635963-3328488,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7635963-3513311,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7635963-3700649,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7635963-3755211,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7635963-387820,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7635963-5501475,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7635963-557521,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7635963-6079762,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7635963-6397562,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7635963-6406495,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7635963-6767236,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7635963-6842086,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7635963-7890651,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7635963-8016137,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7635963-8048962,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7635963-8087941,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7635963-8139578,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7635963-8175805,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7635963-8181144,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7635963-8182140,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7635963-8232306,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7635963-8245716,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7635963-8301233,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7635963-8349814,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7635963-8349823,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7635963-8354954,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7635963-8359688,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7635963-8405996,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7635963-845503,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7635963-8464893,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7635963-886304
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0021-9738
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
96
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
700-9
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
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