Document Detail


Inhibiting C-reactive protein for the treatment of cardiovascular disease: promising evidence from rodent models.
MedLine Citation:
PMID:  24803739     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Raised blood C-reactive protein (CRP) level is a predictor of cardiovascular events, but whether blood CRP is causal in the disease process is unknown. The latter would best be defined by pharmacological inhibition of the protein in the context of a randomized case-control study. However, no CRP specific drug is currently available so such a prospective study cannot be performed. Blood CRP is synthesized primarily in the liver and the liver is an organ where antisense oligonucleotide (ASO) drugs accumulate. Taking advantage of this we evaluated the efficacy of CRP specific ASOs in rodents with experimentally induced cardiovascular damage. Treating rats for 4 weeks with a rat CRP-specific ASO achieved >60% reduction of blood CRP. Notably, this effect was associated with improved heart function and pathology following myocardial infarction (induced by ligation of the left anterior descending artery). Likewise in human CRP transgenic mice treated for 2 weeks with a human CRP-specific ASO, blood human CRP was reduced by >70% and carotid artery patency was improved (2 weeks after surgical ligation). CRP specific ASOs might pave the way towards a placebo-controlled trial that could clarify the role of CRP in cardiovascular disease.
Authors:
Alexander J Szalai; Mark A McCrory; Dongqi Xing; Fadi G Hage; Andrew Miller; Suzanne Oparil; Yiu-Fai Chen; Michelle Mazzone; Richard Early; Scott P Henry; Thomas A Zanardi; Mark J Graham; Rosanne M Crooke
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Publication Detail:
Type:  Journal Article     Date:  2014-04-02
Journal Detail:
Title:  Mediators of inflammation     Volume:  2014     ISSN:  1466-1861     ISO Abbreviation:  Mediators Inflamm.     Publication Date:  2014  
Date Detail:
Created Date:  2014-05-07     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9209001     Medline TA:  Mediators Inflamm     Country:  United States    
Other Details:
Languages:  eng     Pagination:  353614     Citation Subset:  IM    
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