| Development of apolipoprotein B antisense molecules as a therapy for hyperlipidemia. | |
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MedLine Citation:
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PMID: 20425272 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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As new studies demonstrate that lower levels of low-density lipoprotein cholesterol (LDL-C) reduce cardiovascular disease, and as goals for LDL-C in high-risk individuals are reduced further and further, reaching those goals becomes more difficult for a significant percentage of the population. New therapeutic approaches to lower LDL-C would, therefore, be advantageous, particularly in those who are most likely to suffer cardiovascular disease-associated morbidity and mortality. Mouse and human genetic models suggest that decreasing hepatic apolipoprotein B (apoB) production may be a therapeutic approach for the treatment of dyslipidemia. Because antisense oligonucleotides naturally distribute to the liver and can specifically inhibit synthesis of proteins from their messenger RNAs, antisense oligonucleotides represent a potential approach for decreasing the biosynthesis of apoB, and thereby, the production of both very low density lipoprotein (VLDL) and LDL. Newly developed apoB antisense approaches have produced results in animal models and humans, providing proof of concept regarding reductions in LDL-C concentrations. Surprisingly, despite prior experience with inhibitors of microsomal triglyceride transfer protein, which also inhibits the secretion of VLDL, apoB antisense-mediated reduction in VLDL secretion does not appear to cause marked steatosis. The mechanisms whereby two different approaches for inhibiting apoB and triglyceride secretion have different effects on hepatic triglycerides are currently being examined. |
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Authors:
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Tiffany Thomas; Henry Ginsberg |
Publication Detail:
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Type: Journal Article; Review |
Journal Detail:
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Title: Current atherosclerosis reports Volume: 12 ISSN: 1534-6242 ISO Abbreviation: Curr Atheroscler Rep Publication Date: 2010 Jan |
Date Detail:
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Created Date: 2010-04-28 Completed Date: 2010-10-05 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100897685 Medline TA: Curr Atheroscler Rep Country: United States |
Other Details:
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Languages: eng Pagination: 58-65 Citation Subset: IM |
Affiliation:
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Columbia University, 622 West 168th Street, PH10-305, New York, NY 10032, USA. tt2254@columbia.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antilipemic Agents / pharmacology* Apolipoproteins B / biosynthesis, chemistry* Drug Design* Humans Hyperlipidemias / drug therapy*, metabolism Liver / secretion Oligonucleotides / pharmacology* |
| Chemical | |
Reg. No./Substance:
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0/Antilipemic Agents; 0/Apolipoproteins B; 0/ISIS 301012; 0/Oligonucleotides |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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