Title: MicroRNA Profiling Identifies MicroRNA-155 as an Adverse Mediator of Cardiac Injury and Dysfunction During Acute Viral Myocarditis
Authors: Corsten, Maarten F ×
Papageorgiou, Anna-Pia
Verhesen, Wouter
Carai, Paolo
Lindow, Morten
Obad, Susanna
Summer, Georg
Coort, Susan L M
Hazebroek, Mark
van Leeuwen, Rick
Gijbels, Marion J J
Wijnands, Erwin
Biessen, Erik A L
De Winther, Menno P J
Stassen, Frank R M
Carmeliet, Peter
Kauppinen, Sakari
Schroen, Blanche
Heymans, Stephane #
Issue Date: Aug-2012
Publisher: Lippincott Williams & Wilkins
Series Title: Circulation research vol:111 issue:4 pages:415-425
Abstract: 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.
ISSN: 0009-7330
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Angiogenesis and Vascular Metabolism (VIB-KU Leuven Centre for Cancer Biology) (+)
× corresponding author
# (joint) last author

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