Document Detail


The influence of PCSK9 polymorphisms on serum low-density lipoprotein cholesterol and risk of atherosclerosis.
MedLine Citation:
PMID:  20623344     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Jean Davignon; Geneviève Dubuc; Nabil G Seidah
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Current atherosclerosis reports     Volume:  12     ISSN:  1534-6242     ISO Abbreviation:  Curr Atheroscler Rep     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-07-29     Completed Date:  2010-11-30     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100897685     Medline TA:  Curr Atheroscler Rep     Country:  United States    
Other Details:
Languages:  eng     Pagination:  308-15     Citation Subset:  IM    
Affiliation:
Hyperlipidemia and Atherosclerosis Research Group, Clinical Research Institute of Montreal (IRCM), 110 Pine Avenue West, Montreal, QC, H2W 1R7, Canada. davignj@ircm.qc.ca
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MeSH Terms
Descriptor/Qualifier:
Atherosclerosis / 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:
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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