Document Detail

MicroRNA Profiling Identifies MicroRNA-155 as an Adverse Mediator of Cardiac Injury and Dysfunction During Acute Viral Myocarditis.
MedLine Citation:
PMID:  22715471     Owner:  NLM     Status:  Publisher    
Rationale:Viral myocarditis results from an adverse immune response to cardiotropic viruses, which causes irreversible myocyte destruction and heart failure in previously healthy people. The involvement of microRNAs and their usefulness as therapeutic targets in this process are unknown.Objective:To identify microRNAs involved in viral myocarditis pathogenesis and susceptibility.Methods and Results:Cardiac microRNAs were profiled in both human myocarditis and in Coxsackievirus B3-injected mice, comparing myocarditis-susceptible with nonsusceptible mouse strains longitudinally. MicroRNA responses diverged depending on the susceptibility to myocarditis after viral infection in mice. MicroRNA-155, -146b, and -21 were consistently and strongly upregulated during acute myocarditis in both humans and susceptible mice. We found that microRNA-155 expression during myocarditis was localized primarily in infiltrating macrophages and T lymphocytes. Inhibition of microRNA-155 by a systemically delivered LNA-antimiR attenuated cardiac infiltration by monocyte-macrophages, decreased T lymphocyte activation, and reduced myocardial damage in acute myocarditis in mice. These changes were accompanied by the derepression of the direct microRNA-155 target PU.1 in cardiac inflammatory cells. Beyond the acute phase, microRNA-155 inhibition reduced mortality and improved cardiac function during 7 weeks of follow-up.Conclusions:Our data show that cardiac microRNA dysregulation is a characteristic of both human and mouse viral myocarditis. The inflammatory microRNA-155 is upregulated during acute myocarditis, contributes to the adverse inflammatory response to viral infection of the heart, and is a potential therapeutic target for viral myocarditis.
Maarten F Corsten; Anna Papageorgiou; Wouter Verhesen; Paolo Carai; Morten Lindow; Susanna Obad; Georg Summer; Susan L M Coort; Mark Hazebroek; Rick van Leeuwen; Marion J J Gijbels; Erwin Wijnands; Erik A L Biessen; Menno P J De Winther; Frank R M Stassen; Peter Carmeliet; Sakari Kauppinen; Blanche Schroen; Stephane Heymans
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-6-19
Journal Detail:
Title:  Circulation research     Volume:  -     ISSN:  1524-4571     ISO Abbreviation:  -     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-6-20     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0047103     Medline TA:  Circ Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Center for Heart Failure Research, Cardiovascular Research Institute Maastricht.
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