Source:http://linkedlifedata.com/resource/pubmed/id/16002740
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
10
|
| pubmed:dateCreated |
2005-10-3
|
| pubmed:abstractText |
The naturally occurring human lipoprotein lipase S447X variant (LPLS447X) exemplifies a gain-of function mutation with significant benefits including decreased plasma triglycerides (TG), increased high-density lipoprotein (HDL) cholesterol, and reduced risk of coronary artery disease. The S447X variant may be associated with higher LPL catalytic activity; however, in vitro data supporting this hypothesis are contradictory. We wanted to investigate the in vivo mechanism by which the LPLS447X variant improves the lipid profile of S447X carriers. We conducted a functional assessment of human LPLS447X compared with LPLWT in mice. LPL variants were compared in the absence of endogenous mouse LPL in newborn LPL(-/-) mice by adenoviral-mediated gene transfer. LPL(-/-) mice normally exhibit severe hypertriglyceridemia and die within 48 hours of birth. LPLWT gene transfer prolonged the survival of mice up to 21 days. In contrast, LPLS447X completely rescued 95% of the mice to adulthood and increased LPL catalytic activity in postheparin plasma 2.1-fold compared with LPLWT at day 3 (P=0.003). LPLS447X also reduced plasma TG 99% from baseline (P<0.001), 2-fold more than LPLWT, (P<0.01) and increased plasma HDL cholesterol 2.9-fold higher than LPLWT (P<0.01). These data provide in vivo evidence that the increased catalytic activity of LPLS447X improves plasma TG clearance and increases the HDL cholesterol pool compared with LPLWT.
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| pubmed:commentsCorrections | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Oct
|
| pubmed:issn |
1524-4636
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| pubmed:author |
pubmed-author:ExcoffonKatherine J D AshbourneKJ,
pubmed-author:HaydenMichael RMR,
pubmed-author:KasteleinJohn JJJ,
pubmed-author:KuivenhovenJan AlbertJA,
pubmed-author:LewisSuzanne M ESM,
pubmed-author:LiuGuoqingG,
pubmed-author:RipJaapJ,
pubmed-author:RossColin J DCJ,
pubmed-author:TwiskJaapJ,
pubmed-author:van DopWillemijnW
|
| pubmed:issnType |
Electronic
|
| pubmed:volume |
25
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
2143-50
|
| pubmed:dateRevised |
2006-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:16002740-Adenoviridae,
pubmed-meshheading:16002740-Animals,
pubmed-meshheading:16002740-Animals, Newborn,
pubmed-meshheading:16002740-CHO Cells,
pubmed-meshheading:16002740-Cholesterol, HDL,
pubmed-meshheading:16002740-Cricetinae,
pubmed-meshheading:16002740-Fertility,
pubmed-meshheading:16002740-Gene Therapy,
pubmed-meshheading:16002740-Gene Transfer Techniques,
pubmed-meshheading:16002740-Humans,
pubmed-meshheading:16002740-Hypertriglyceridemia,
pubmed-meshheading:16002740-Lactation,
pubmed-meshheading:16002740-Lipoprotein Lipase,
pubmed-meshheading:16002740-Mice,
pubmed-meshheading:16002740-Mice, Inbred C57BL,
pubmed-meshheading:16002740-Mice, Mutant Strains,
pubmed-meshheading:16002740-Point Mutation,
pubmed-meshheading:16002740-RNA, Messenger,
pubmed-meshheading:16002740-Triglycerides
|
| pubmed:year |
2005
|
| pubmed:articleTitle |
Complete rescue of lipoprotein lipase-deficient mice by somatic gene transfer of the naturally occurring LPLS447X beneficial mutation.
|
| pubmed:affiliation |
Department of Medical Genetics, University of British Columbia, Centre for Molecular Medicine and Therapeutics, Vancouver, Canada.
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|