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Mediators of Inflammation
Volume 2014 (2014), Article ID 353614, 9 pages
http://dx.doi.org/10.1155/2014/353614
Research Article

Inhibiting C-Reactive Protein for the Treatment of Cardiovascular Disease: Promising Evidence from Rodent Models

1Division of Clinical Immunology and Rheumatology, Department of Medicine, The University of Alabama at Birmingham, 1825 University Boulevard, SHEL 214, Birmingham, Al 35294-2182, USA
2Division of Cardiovascular Disease, The University of Alabama at Birmingham, Birmingham, AL 35294-0006, USA
3Charles River Laboratories, Sparks, NV 89431, USA
4Isis Pharmaceuticals, 2855 Gazelle Court, Carlsbad, CA 92008, USA

Received 15 January 2014; Accepted 28 February 2014; Published 2 April 2014

Academic Editor: Jan Torzewski

Copyright © 2014 Alexander J. Szalai et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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.