ITEM METADATA RECORD
Title: Macrophage MicroRNA-155 Promotes Cardiac Hypertrophy and Failure
Authors: Heymans, Stephane ×
Corsten, Maarten F
Verhesen, Wouter
Carai, Paolo
van Leeuwen, Rick E. W
Custers, Kevin
Peters, Tim
Hazebroek, Mark
Stoeger, Lauran
Wijnands, Erwin
Janssen, Ben J
Creemers, Esther E
Pinto, Yigal M
Grimm, Dirk
Schuermann, Nina
Vigorito, Elena
Thum, Thomas
Stassen, Frank
Yin, Xiaoke
Mayr, Manuel
de Windt, Leon J
Lutgens, Esther
Wouters, Kristiaan
de Winther, Menno P. J
Zacchigna, Serena
Giacca, Mauro
van Bilsen, Marc
Papageorgiou, Anna-Pia
Schroen, Blanche #
Issue Date: 2013
Publisher: Lippincott Williams & Wilkins
Series Title: Circulation vol:128 issue:13 pages:1420-1432
Abstract: BACKGROUND:
Cardiac hypertrophy and subsequent heart failure triggered by chronic hypertension represent major challenges for cardiovascular research. Beyond neurohormonal and myocyte signaling pathways, growing evidence suggests inflammatory signaling pathways as therapeutically targetable contributors to this process. We recently reported that microRNA-155 is a key mediator of cardiac inflammation and injury in infectious myocarditis. Here, we investigated the impact of microRNA-155 manipulation in hypertensive heart disease.
METHODS AND RESULTS:
Genetic loss or pharmacological inhibition of the leukocyte-expressed microRNA-155 in mice markedly reduced cardiac inflammation, hypertrophy, and dysfunction on pressure overload. These alterations were macrophage dependent because in vivo cardiomyocyte-specific microRNA-155 manipulation did not affect cardiac hypertrophy or dysfunction, whereas bone marrow transplantation from wild-type mice into microRNA-155 knockout animals rescued the hypertrophic response of the cardiomyocytes and vice versa. In vitro, media from microRNA-155 knockout macrophages blocked the hypertrophic growth of stimulated cardiomyocytes, confirming that macrophages influence myocyte growth in a microRNA-155-dependent paracrine manner. These effects were at least partly mediated by the direct microRNA-155 target suppressor of cytokine signaling 1 (Socs1) because Socs1 knockdown in microRNA-155 knockout macrophages largely restored their hypertrophy-stimulating potency.
CONCLUSIONS:
Our findings reveal that microRNA-155 expression in macrophages promotes cardiac inflammation, hypertrophy, and failure in response to pressure overload. These data support the causative significance of inflammatory signaling in hypertrophic heart disease and demonstrate the feasibility of therapeutic microRNA targeting of inflammation in heart failure.
ISSN: 0009-7322
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular and Vascular Biology
× corresponding author
# (joint) last author

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