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Comparison of IL-10 and MCP-1-7ND gene transfer with AAV9 vectors for protection from murine autoimmune myocarditis

Overexpression of therapeutic genes with potential disease-limiting effects, specifically at the site of inflammation, remains a major clinical challenge. In this study, we investigate the potential of adeno-associated virus (AAV)-9-mediated cardiac expression of the anti-inflammatory mediators inte...

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Main Authors: Kaya, Ziya (Author) , Leib, Christoph (Author) , Werfel, Stanislas (Author) , Göser, Stefan (Author) , Öttl, Renate (Author) , Leuchs, Barbara (Author) , Pfitzer, Gabriele (Author) , Katus, Hugo (Author) , Müller, Oliver J. (Author)
Format: Article (Journal)
Language:English
Published: 25 February 2011
In: Cardiovascular research
Year: 2011, Volume: 91, Issue: 1, Pages: 116-123
ISSN:1755-3245
DOI:10.1093/cvr/cvr063
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1093/cvr/cvr063
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Author Notes:Ziya Kaya, Christoph Leib, Stanislas Werfel, Stefan Göser, Renate Öttl, Barbara Leuchs, Gabriele Pfitzer, Hugo A. Katus, and Oliver J. Müller
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Summary:Overexpression of therapeutic genes with potential disease-limiting effects, specifically at the site of inflammation, remains a major clinical challenge. In this study, we investigate the potential of adeno-associated virus (AAV)-9-mediated cardiac expression of the anti-inflammatory mediators interleukin (IL)-10 and a dominant-negative inhibitor of monocyte chemoattractant protein-1 (MCP1-7ND) on prevention of autoimmune myocarditis.Autoimmune myocarditis was induced by immunizing A/J mice with subcutaneous injection of 120 µg cardiac Troponin I (cTnI) on Days 0, 7, and 14. Two weeks prior to initial immunization, each mouse received a single systemic dose of 1012 AAV9 vectors carrying the coding sequence of IL-10 or MCP1-7ND transcriptionally targeted to the heart. Mice were sacrificed 28 days after initial immunization for further analysis. Only expression of IL-10 resulted in a highly significant decrease in myocardial inflammation and fibrosis, as well as an increased ejection fraction compared with controls. Further analyses of cytokine profiles of cTnI-stimulated splenocytes from IL-10 and MCP1-7ND-treated mice revealed significant alterations compared with controls. In addition, transcript levels of chemokine receptor CCR4 and T-cell activation gene were significantly reduced in hearts of IL-10-treated mice as determined by quantitative real-time PCR.Our study suggests that cardiac expression of IL-10 with AAV9 vectors is a promising therapeutic approach for autoimmune myocarditis.
Item Description:Gesehen am 25.07.2022
Physical Description:Online Resource
ISSN:1755-3245
DOI:10.1093/cvr/cvr063

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