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http://purl.uniprot.org/citations/22705886http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/22705886http://www.w3.org/2000/01/rdf-schema#comment"

Background

Inflammation plays a critical role in adverse cardiac remodeling and heart failure. Therefore, approaches geared toward inhibiting inflammation may provide therapeutic benefits. We tested the hypotheses that genetic deletion of interleukin-10 (IL-10), a potent antiinflammatory cytokine, exacerbates pressure overload-induced adverse cardiac remodeling and hypertrophy and that IL-10 therapy inhibits this pathology.

Methods and results

Cardiac hypertrophy was induced in wild-type and IL-10 knockout mice by isoproterenol (ISO) infusion. ISO-induced left ventricular dysfunction and hypertrophic remodeling, including fibrosis and fetal gene expression, were further exaggerated in knockout mice compared with wild-type mice. Systemic recombinant mouse IL-10 administration markedly improved left ventricular function and not only inhibited but also reversed ISO-induced cardiac remodeling. Intriguingly, a very similar cardioprotective response of IL-10 was found in transverse aortic constriction-induced hypertrophy and heart failure models. In neonatal rat ventricular myocytes and H9c2 myoblasts, ISO activated nuclear factor-κB and inhibited signal transducers and activators of transcription 3 (STAT3) phosphorylation. Interestingly, IL-10 suppressed ISO-induced nuclear factor-κB activation and attenuated STAT3 inhibition. Moreover, pharmacological and genetic inhibition of STAT3 reversed the protective effects of IL-10, whereas ectopic expression of constitutively active STAT3 mimicked the IL-10 responses on the ISO effects, confirming that the IL-10-mediated inhibition of nuclear factor-κB is STAT3 dependent.

Conclusion

Taken together, our results suggest IL-10 treatment as a potential therapeutic approach to limit the progression of pressure overload-induced adverse cardiac remodeling."xsd:string
http://purl.uniprot.org/citations/22705886http://purl.org/dc/terms/identifier"doi:10.1161/circulationaha.112.112185"xsd:string
http://purl.uniprot.org/citations/22705886http://purl.uniprot.org/core/author"Gupta R."xsd:string
http://purl.uniprot.org/citations/22705886http://purl.uniprot.org/core/author"Singh N."xsd:string
http://purl.uniprot.org/citations/22705886http://purl.uniprot.org/core/author"Ghosh A.K."xsd:string
http://purl.uniprot.org/citations/22705886http://purl.uniprot.org/core/author"Qin G."xsd:string
http://purl.uniprot.org/citations/22705886http://purl.uniprot.org/core/author"Krishnamurthy P."xsd:string
http://purl.uniprot.org/citations/22705886http://purl.uniprot.org/core/author"Ramirez V."xsd:string
http://purl.uniprot.org/citations/22705886http://purl.uniprot.org/core/author"Verma S.K."xsd:string
http://purl.uniprot.org/citations/22705886http://purl.uniprot.org/core/author"Hoxha E."xsd:string
http://purl.uniprot.org/citations/22705886http://purl.uniprot.org/core/author"Kishore R."xsd:string
http://purl.uniprot.org/citations/22705886http://purl.uniprot.org/core/author"Mackie A."xsd:string
http://purl.uniprot.org/citations/22705886http://purl.uniprot.org/core/author"Sadayappan S."xsd:string
http://purl.uniprot.org/citations/22705886http://purl.uniprot.org/core/author"Barefield D."xsd:string
http://purl.uniprot.org/citations/22705886http://purl.uniprot.org/core/author"Lambers E."xsd:string
http://purl.uniprot.org/citations/22705886http://purl.uniprot.org/core/author"Thal M."xsd:string
http://purl.uniprot.org/citations/22705886http://purl.uniprot.org/core/date"2012"xsd:gYear
http://purl.uniprot.org/citations/22705886http://purl.uniprot.org/core/name"Circulation"xsd:string
http://purl.uniprot.org/citations/22705886http://purl.uniprot.org/core/pages"418-429"xsd:string
http://purl.uniprot.org/citations/22705886http://purl.uniprot.org/core/title"Interleukin-10 treatment attenuates pressure overload-induced hypertrophic remodeling and improves heart function via signal transducers and activators of transcription 3-dependent inhibition of nuclear factor-kappaB."xsd:string
http://purl.uniprot.org/citations/22705886http://purl.uniprot.org/core/volume"126"xsd:string
http://purl.uniprot.org/citations/22705886http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/22705886
http://purl.uniprot.org/citations/22705886http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/22705886
http://purl.uniprot.org/uniprot/#_A0A7R8GUQ3-mappedCitation-22705886http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/22705886
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