NF- B activation is required for adaptive cardiac hypertrophy

Zelarayán, Laura C.; Renger, Anke; Noack, Claudia; Zafiriou, Maria-Patapia; Gehrke, Christina; Nagel, Roel van der; Dietz, Rainer; Windt, León J. De; Bergmann, Martin

doi:10.1093/cvr/cvp237

Cited by 76 publications

(50 citation statements)

References 15 publications

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“…NF-B has been implicated in cardiac hypertrophy, and the best evidence is from a transgenic mouse model with cardiac-specific expression of a mutant IB␣ that acts as a super-repressor of NF-B (30, 31). The expression of this mutant attenuated hypertrophic phenotypes induced by angiotensin II or isoproterenol infusion as well as aortic banding (34,35). The fetal gene program was also abrogated in this model and therefore, irrespective of whether these two molecules can interact at the protein level in the cytoplasm (14 -17), NF-B and GRK5 activity in the heart may lead to inter-related or parallel hypertrophic gene transcriptional paths.…”

Section: Discussionmentioning

confidence: 92%

Involvement of Nuclear Factor κB (NF-κB) Signaling Pathway in Regulation of Cardiac G Protein-coupled Receptor Kinase 5 (GRK5) Expression

Islam

Koch²

2012

Journal of Biological Chemistry

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Background: GRK5 up-regulation and NF-B activation have been shown to be associated with heart disease. Results: NF-B activation in cardiomyocytes promotes stress-induced GRK5 up-regulation. Conclusion: NF-B activation by hypertrophic stimuli/ROS leads to increased binding of NF-B (p50/p65) to the GRK5 promoter, thereby enhancing myocardial GRK5 expression. Significance: NF-B regulation of GRK5 in myocytes may translate to the significant expression changes seen in heart disease.

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Section: Discussionmentioning

confidence: 92%

Involvement of Nuclear Factor κB (NF-κB) Signaling Pathway in Regulation of Cardiac G Protein-coupled Receptor Kinase 5 (GRK5) Expression

Islam

Koch²

2012

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 97%

Regulation of Nuclear Factor κB (NF-κB) in the Nucleus of Cardiomyocytes by G Protein-coupled Receptor Kinase 5 (GRK5)

Islam

Bae

Gao

et al. 2013

Journal of Biological Chemistry

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Background: NF-B activation and GRK5 up-regulation have been shown to be associated with heart disease. Results: GRK5 induces NF-B signaling pathway both in cardiomyocytes and in mouse hearts. Conclusion: GRK5 triggers the binding of NF-B (p50/p65) to DNA in the nucleus and promotes gene transcription including hypertrophic gene. Significance: GRK5 up-regulation may lead to a significant increase in expression and activation of NF-B seen in heart disease.

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“…Previous studies have established that NF-κB is required for cardiac hypertrophy, but is dispensable for normal heart structure and function (8,10,11,27). Our finding that activation of IKK/NF-κB in the heart primarily induces cardiomyocyte atrophy rather than hypertrophy is not necessarily a contradiction to these studies, as the biological function of IKK/NF-κB may depend on the strength of activation and/or on context, and on the component of the IKK/NF-κB system that is manipulated.…”

Section: Role Of Chemokines Cytokines Adhesion Molecules and Myd88mentioning

confidence: 99%

“…The function of IKK/NF-κB during ischemia/reperfusion injury, myocardial infarction, and subsequent remodeling processes is controversial (1,2). As to myocyte growth, IKK/NF-κB activation in vivo is required for certain forms of hypertrophy (8)(9)(10)(11), but not for others (6,7).…”

mentioning

confidence: 99%

Cardiomyocyte-specific IκB kinase (IKK)/NF-κB activation induces reversible inflammatory cardiomyopathy and heart failure

Maier

Schips²,

Wietelmann³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

156

117

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Inflammation is a major factor in heart disease. IκB kinase (IKK) and its downstream target NF-κB are regulators of inflammation and are activated in cardiac disorders, but their precise contributions and targets are unclear. We analyzed IKK/NF-κB function in the heart by a gain-of-function approach, generating an inducible transgenic mouse model with cardiomyocyte-specific expression of constitutively active IKK2. In adult animals, IKK2 activation led to inflammatory dilated cardiomyopathy and heart failure. Transgenic hearts showed infiltration with CD11b + cells, fibrosis, fetal reprogramming, and atrophy of myocytes with strong constitutively active IKK2 expression. Upon transgene inactivation, the disease was reversible even at an advanced stage. IKK-induced cardiomyopathy was dependent on NF-κB activation, as in vivo expression of IκBα superrepressor, an inhibitor of NF-κB, prevented the development of disease. Gene expression and proteomic analyses revealed enhanced expression of inflammatory cytokines, and an IFN type I signature with activation of the IFN-stimulated gene 15 (ISG15) pathway. In that respect, IKK-induced cardiomyopathy resembled Coxsackievirus-induced myocarditis, during which the NF-κB and ISG15 pathways were also activated. Vice versa, in cardiomyocytes lacking the regulatory subunit of IKK (IKKγ/NEMO), the induction of ISG15 was attenuated. We conclude that IKK/NF-κB activation in cardiomyocytes is sufficient to cause cardiomyopathy and heart failure by inducing an excessive inflammatory response and myocyte atrophy.transcription factors | transgenic mice

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NF- B activation is required for adaptive cardiac hypertrophy

Abstract: NF-kappaB inhibition attenuates cardiac hypertrophy in a gender-specific manner but does not alter the course of stress-induced LV remodelling, indicating NF-kappaB to be required for adaptive cardiac hypertrophy.

Cited by 76 publications

References 15 publications

Involvement of Nuclear Factor κB (NF-κB) Signaling Pathway in Regulation of Cardiac G Protein-coupled Receptor Kinase 5 (GRK5) Expression

Involvement of Nuclear Factor κB (NF-κB) Signaling Pathway in Regulation of Cardiac G Protein-coupled Receptor Kinase 5 (GRK5) Expression

Regulation of Nuclear Factor κB (NF-κB) in the Nucleus of Cardiomyocytes by G Protein-coupled Receptor Kinase 5 (GRK5)

Cardiomyocyte-specific IκB kinase (IKK)/NF-κB activation induces reversible inflammatory cardiomyopathy and heart failure

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