| The influence of PCSK9 polymorphisms on serum low-density lipoprotein cholesterol and risk of atherosclerosis. | |
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MedLine Citation:
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PMID: 20623344 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Pro-protein-convertase-subtilisin-kexin-9 (PCSK9) enhances the degradation of the low-density lipoprotein receptor (LDLR) that plays a major role in cholesterol homeostasis. Recent advances have revealed a large number of genetic variants of PCSK9 that may modulate plasma cholesterol levels either positively or negatively, therefore influencing the risk of atherosclerosis. Recognition of these mutants may have clinical implication in assessing severity of disease, prognosis, or response to drug therapy. PCSK9's expression, secretion, and plasma levels maybe modulated by the proprotein convertase furin, by natural inhibitors (annexin-A2), or influenced by lipid-altering agents such as statins, fibrates, ezetimibe, and berberine. It is now a prime target for therapy, prompting the development of various approaches to reduce its LDLR degrading activity, including antibody neutralization, anti-sense oligonucleotides such as phosphorothioates, locked nucleic acids, and RNA interference, and eventually small molecule inhibitors. Which one will be clinically applicable will depend on long-term effects, cost, and ease of administration. |
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Authors:
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Jean Davignon; Geneviève Dubuc; Nabil G Seidah |
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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 Sep |
Date Detail:
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Created Date: 2010-07-29 Completed Date: 2010-11-30 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: 308-15 Citation Subset: IM |
Affiliation:
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Hyperlipidemia and Atherosclerosis Research Group, Clinical Research Institute of Montreal (IRCM), 110 Pine Avenue West, Montreal, QC, H2W 1R7, Canada. davignj@ircm.qc.ca |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Atherosclerosis
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blood,
genetics* Cholesterol, LDL / blood* Disease Progression Genetic Predisposition to Disease* Humans Polymorphism, Genetic* RNA / genetics* Risk Factors Serine Endopeptidases / blood, genetics* |
| Chemical | |
Reg. No./Substance:
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0/Cholesterol, LDL; 63231-63-0/RNA; EC 3.4.21.-/PCSK9 protein, human; EC 3.4.21.-/Serine Endopeptidases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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