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

• Verfasst von: Kaya, Ziya [VerfasserIn]
• Verfasst von: Leib, Christoph [VerfasserIn]
• Verfasst von: Werfel, Stanislas [VerfasserIn]
• Verfasst von: Göser, Stefan [VerfasserIn]
• Verfasst von: Öttl, Renate [VerfasserIn]
• Verfasst von: Leuchs, Barbara [VerfasserIn]
• Verfasst von: Pfitzer, Gabriele [VerfasserIn]
• Verfasst von: Katus, Hugo [VerfasserIn]
• Verfasst von: Müller, Oliver J. [VerfasserIn]
• Titel: Comparison of IL-10 and MCP-1-7ND gene transfer with AAV9 vectors for protection from murine autoimmune myocarditis
• Verf.angabe: Ziya Kaya, Christoph Leib, Stanislas Werfel, Stefan Göser, Renate Öttl, Barbara Leuchs, Gabriele Pfitzer, Hugo A. Katus, and Oliver J. Müller
• E-Jahr: 2011
• Jahr: 25 February 2011
• Umfang: 8 S.
• Fussnoten: Gesehen am 25.07.2022
• Titel Quelle: Enthalten in: Cardiovascular research
• Ort Quelle: Oxford : Oxford University Press, 1967
• Jahr Quelle: 2011
• Band/Heft Quelle: 91(2011), 1, Seite 116-123
• ISSN Quelle: 1755-3245
• DOI: doi:10.1093/cvr/cvr063
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1811470432

Abstract

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.