Document Detail


PCSK9 Inhibitors: Potential in Cardiovascular Therapeutics.
MedLine Citation:
PMID:  23338726     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Despite the efficacy of statin therapy, patients treated with these agents face substantial residual risk that is associated with achieved levels of LDL cholesterol (LDL-C). These observations suggest a potential benefit of additional strategies to promote further LDL-C reduction. Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as an attractive target in this regard. Abrogation of PCSK9 function prevents PCSK9-mediated catabolism of LDL receptors, increases cell surface LDL receptor density, and promotes clearance of LDL and other atherogenic lipoproteins from the circulation. Thus far, the most advanced approaches to block PCSK9 action are monoclonal antibodies and anti-sense oligonucleotides. Among statin-treated patients, these agents may produce additional LDL-C lowering exceeding 50 %. In rare genetic experiments of nature, individuals with dominant negative or dual loss of function mutations of PCSK9 appear to have no adverse health effects resulting from lifelong, very low levels of LDL-C. In short-term trials, PCSK9 antibodies have been generally well-tolerated. However, evidence to support long-term safety and efficacy of PCSK9 therapy to reduce cardiovascular risk awaits the results of large cardiovascular outcome trials.
Authors:
Rose Q Do; Robert A Vogel; Gregory G Schwartz
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Current cardiology reports     Volume:  15     ISSN:  1534-3170     ISO Abbreviation:  Curr Cardiol Rep     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-01-22     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100888969     Medline TA:  Curr Cardiol Rep     Country:  United States    
Other Details:
Languages:  eng     Pagination:  345     Citation Subset:  IM    
Affiliation:
VA Medical Center, Denver, CO, 80220, USA.
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