Inhibiting C-Reactive Protein for the Treatment of Cardiovascular Disease: Promising Evidence from Rodent Models
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 spe...
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| Format: | Article |
| Language: | English |
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Wiley
2014-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2014/353614 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Alexander J. Szalai |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-1353b401cb894bb4a6035781bd29725d |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-1353b401cb894bb4a6035781bd29725d2025-02-03T01:29:16ZengWileyMediators of Inflammation0962-93511466-18612014-01-01201410.1155/2014/353614353614Inhibiting C-Reactive Protein for the Treatment of Cardiovascular Disease: Promising Evidence from Rodent ModelsAlexander J. Szalai0Mark A. McCrory1Dongqi Xing2Fadi G. Hage3Andrew Miller4Suzanne Oparil5Yiu-Fai Chen6Michelle Mazzone7Richard Early8Scott P. Henry9Thomas A. Zanardi10Mark J. Graham11Rosanne M. Crooke12Division of Clinical Immunology and Rheumatology, Department of Medicine, The University of Alabama at Birmingham, 1825 University Boulevard, SHEL 214, Birmingham, Al 35294-2182, USADivision of Clinical Immunology and Rheumatology, Department of Medicine, The University of Alabama at Birmingham, 1825 University Boulevard, SHEL 214, Birmingham, Al 35294-2182, USADivision of Cardiovascular Disease, The University of Alabama at Birmingham, Birmingham, AL 35294-0006, USADivision of Cardiovascular Disease, The University of Alabama at Birmingham, Birmingham, AL 35294-0006, USADivision of Cardiovascular Disease, The University of Alabama at Birmingham, Birmingham, AL 35294-0006, USADivision of Cardiovascular Disease, The University of Alabama at Birmingham, Birmingham, AL 35294-0006, USADivision of Cardiovascular Disease, The University of Alabama at Birmingham, Birmingham, AL 35294-0006, USACharles River Laboratories, Sparks, NV 89431, USACharles River Laboratories, Sparks, NV 89431, USAIsis Pharmaceuticals, 2855 Gazelle Court, Carlsbad, CA 92008, USAIsis Pharmaceuticals, 2855 Gazelle Court, Carlsbad, CA 92008, USAIsis Pharmaceuticals, 2855 Gazelle Court, Carlsbad, CA 92008, USAIsis Pharmaceuticals, 2855 Gazelle Court, Carlsbad, CA 92008, USARaised 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.http://dx.doi.org/10.1155/2014/353614 |
| spellingShingle | 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 Inhibiting C-Reactive Protein for the Treatment of Cardiovascular Disease: Promising Evidence from Rodent Models Mediators of Inflammation |
| title | Inhibiting C-Reactive Protein for the Treatment of Cardiovascular Disease: Promising Evidence from Rodent Models |
| title_full | Inhibiting C-Reactive Protein for the Treatment of Cardiovascular Disease: Promising Evidence from Rodent Models |
| title_fullStr | Inhibiting C-Reactive Protein for the Treatment of Cardiovascular Disease: Promising Evidence from Rodent Models |
| title_full_unstemmed | Inhibiting C-Reactive Protein for the Treatment of Cardiovascular Disease: Promising Evidence from Rodent Models |
| title_short | Inhibiting C-Reactive Protein for the Treatment of Cardiovascular Disease: Promising Evidence from Rodent Models |
| title_sort | inhibiting c reactive protein for the treatment of cardiovascular disease promising evidence from rodent models |
| url | http://dx.doi.org/10.1155/2014/353614 |
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