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The E3 ubiquitin ligase HectD3 attenuates cardiac hypertrophy and inflammation in mice

Myocardial inflammation has recently been recognized as a distinct feature of cardiac hypertrophy and heart failure. HectD3, a HECT domain containing E3 ubiquitin ligase has previously been investigated in the host defense against infections as well as neuroinflammation; its cardiac function however...

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Main Authors: Rangrez, Ashraf Yusuf (Author) , Borlepawar, Ankush (Author) , Schmiedel, Nesrin (Author) , Deshpande, Anushka (Author) , Remes, Anca (Author) , Kumari, Manju (Author) , Bernt, Alexander (Author) , Christen, Lynn (Author) , Helbig, Andreas (Author) , Jungmann, Andreas (Author) , Sossalla, Samuel (Author) , Tholey, Andreas (Author) , Müller, Oliver J. (Author) , Frank, Derk (Author) , Frey, Norbert (Author)
Format: Article (Journal)
Language:English
Published: 09 October 2020
In: Communications biology
Year: 2020, Volume: 3, Pages: 1-15
ISSN:2399-3642
DOI:10.1038/s42003-020-01289-2
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/s42003-020-01289-2
Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/s42003-020-01289-2
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Author Notes:Ashraf Yusuf Rangrez, Ankush Borlepawar, Nesrin Schmiedel, Anushka Deshpande, Anca Remes, Manju Kumari, Alexander Bernt, Lynn Christen, Andreas Helbig, Andreas Jungmann, Samuel Sossalla, Andreas Tholey, Oliver J. Müller, Derk Frank & Norbert Frey
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Summary:Myocardial inflammation has recently been recognized as a distinct feature of cardiac hypertrophy and heart failure. HectD3, a HECT domain containing E3 ubiquitin ligase has previously been investigated in the host defense against infections as well as neuroinflammation; its cardiac function however is still unknown. Here we show that HectD3 simultaneously attenuates Calcineurin-NFAT driven cardiomyocyte hypertrophy and the pro-inflammatory actions of LPS/interferon-γ via its cardiac substrates SUMO2 and Stat1, respectively. AAV9-mediated overexpression of HectD3 in mice in vivo not only reduced cardiac SUMO2/Stat1 levels and pathological hypertrophy but also largely abolished macrophage infiltration and fibrosis induced by pressure overload. Taken together, we describe a novel cardioprotective mechanism involving the ubiquitin ligase HectD3, which links anti-hypertrophic and anti-inflammatory effects via dual regulation of SUMO2 and Stat1. In a broader perspective, these findings support the notion that cardiomyocyte growth and inflammation are more intertwined than previously anticipated.
Item Description:Gesehen am 02.12.2020
Physical Description:Online Resource
ISSN:2399-3642
DOI:10.1038/s42003-020-01289-2

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