Source:http://linkedlifedata.com/resource/pubmed/id/17468777
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
7
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| pubmed:dateCreated |
2007-6-14
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| pubmed:abstractText |
Coxsackievirus B3 (CVB3) is the most common causative agent of infectious myocarditis. Chronic inflammation, loss of contractile tissue, and maladaptive remodeling all contribute to dilated cardiomyopathy and heart failure. The 4-1BB receptor is a costimulatory molecule expressed by T cells and cardiomyocytes. We infected mice with CVB3 to examine if virus infection triggers 4-1BB activation and whether inhibition of this pathway will reduce inflammation and improve heart function. Echocardiography was performed on days 3, 9, 30 and at 10 weeks post-infection (pi) and ejection fraction (EF), left ventricular (LV) wall thickness, contractility, and internal cardiac dimensions were measured. At day 9, reduced rate of wall thickening (30+/-17 vs 70+/-19%), increased LV wall thickness (0.15+/-0.04 vs 0.09+/-0.01 cm in diastole and 0.19+/-0.04 vs 0.15+/-0.02 cm in systole), and reduced cardiac volume (0.013+/-0.004 vs 0.023+/-0.003 ml in diastole and 0.004+/-0.002 ml vs 0.007+/-0.001 ml in systole) were observed in infected hearts as compared with shams. At 14 days pi, CVB3-infected mice were randomly assigned to receive either anti-4-1BBL neutralizing (M522) or control antibodies (Ab) for 8 weeks. Cardiac damage, fibrosis, and inflammation were assessed by histological stains and immunohistochemistry. Polymerase chain reaction (PCR) was utilized to detect matrix metalloproteinase (MMP)-2, MMP-9, and MMP-12 expressions. At 10 weeks pi, M522 treatment improved LV wall thickening rate (-10+/-13 vs -49+/-16%, expressed as percentage change from baseline) and reduced diastolic LV posterior wall thickness (17+/-10 vs 57+/-47%, expressed as percentage change from baseline), cardiac damage as assessed by histological scores (0 vs 1.3+/-1.5), fibrosis by collagen volume fraction (3.2+/-0.6 vs 4.9+/-2.2%), overall inflammation (5.9+/-1.3 vs 8.5+/-4.1%), and T-cell infiltration (1.3+/-0.9 vs 4.3+/-3.8%) as compared to control. MMP-12 was highly increased during acute and chronic myocarditis, but was significantly decreased by M522 treatment. Thus, long-term inhibition of the 4-1BB pathway reduces cardiac damage, remodeling, and inflammation during viral myocarditis.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Jul
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| pubmed:issn |
0023-6837
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
87
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
651-61
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| pubmed:meshHeading |
pubmed-meshheading:17468777-4-1BB Ligand,
pubmed-meshheading:17468777-Animals,
pubmed-meshheading:17468777-Antibodies, Monoclonal,
pubmed-meshheading:17468777-Cardiac Volume,
pubmed-meshheading:17468777-Cardiomyopathy, Dilated,
pubmed-meshheading:17468777-Cell Line,
pubmed-meshheading:17468777-Coxsackievirus Infections,
pubmed-meshheading:17468777-Diastole,
pubmed-meshheading:17468777-Heart Ventricles,
pubmed-meshheading:17468777-Humans,
pubmed-meshheading:17468777-Immunohistochemistry,
pubmed-meshheading:17468777-Male,
pubmed-meshheading:17468777-Matrix Metalloproteinases,
pubmed-meshheading:17468777-Mice,
pubmed-meshheading:17468777-Mice, Inbred Strains,
pubmed-meshheading:17468777-Myocarditis,
pubmed-meshheading:17468777-Myocardium,
pubmed-meshheading:17468777-Pilot Projects,
pubmed-meshheading:17468777-Systole,
pubmed-meshheading:17468777-Ventricular Remodeling
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| pubmed:year |
2007
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| pubmed:articleTitle |
Neutralizing anti-4-1BBL treatment improves cardiac function in viral myocarditis.
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| pubmed:affiliation |
Department of Pathology and Laboratory Medicine, The James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, St Paul's Hospital/Providence Health Care, University of British Columbia, Vancouver, BC, Canada.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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