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AAV6.βARKct cardiac gene therapy ameliorates cardiac function and normalizes the catecholaminergic axis in a clinically relevant large animal heart failure model

Aims: G protein-coupled receptor kinase 2 (GRK2), which is markedly upregulated in failing human myocardium, has been implicated as a contributing factor or consequence of heart failure (HF). Importantly, cardiac-specific GRK2 knockout mice have recently proved the pathological nature of GRK2 in HF....

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Main Authors: Raake, Philip (Author) , Schlegel, Philipp (Author) , Reinkober, Julia (Author) , Barthelmes, Jens (Author) , Schinkel, Stefanie (Author) , Pleger, Sven Torsten (Author) , Mier, Walter (Author) , Haberkorn, Uwe (Author) , Katus, Hugo (Author) , Most, Patrick (Author) , Müller, Oliver J. (Author)
Format: Article (Journal)
Language:English
Published: 2013
In: European heart journal
Year: 2013, Volume: 34, Issue: 19, Pages: 1437-1447
ISSN:1522-9645
DOI:10.1093/eurheartj/ehr447
Online Access:Verlag, Volltext: http://dx.doi.org/10.1093/eurheartj/ehr447
Verlag, Volltext: https://academic.oup.com/eurheartj/article/34/19/1437/422831
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Author Notes:Philip W.J. Raake, Philipp Schlegel, Jan Ksienzyk, Julia Reinkober, Jens Barthelmes, Stefanie Schinkel, Sven Pleger, Walter Mier, Uwe Haberkorn, Walter J. Koch, Hugo A. Katus, Patrick Most, and Oliver J. Müller
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Summary:Aims: G protein-coupled receptor kinase 2 (GRK2), which is markedly upregulated in failing human myocardium, has been implicated as a contributing factor or consequence of heart failure (HF). Importantly, cardiac-specific GRK2 knockout mice have recently proved the pathological nature of GRK2 in HF. Targeted inhibition of GRK2 is possible using a peptide inhibitor known as the βARKct, which has rescued several disparate small animal HF models. This study was designed to evaluate long-term βARKct expression in a clinically relevant large animal HF model, using stable myocardial gene delivery with adeno-associated virus serotype 6 (AAV6).
Item Description:Online publish-ahead-of-print 19 January 2012
Gesehen am 19.11.2018
Physical Description:Online Resource
ISSN:1522-9645
DOI:10.1093/eurheartj/ehr447

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