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Requirement of nuclear factor-kappaB in angiotensin II- and isoproterenol-induced cardiac hypertrophy in vivo

Item Type:Article
Title:Requirement of nuclear factor-kappaB in angiotensin II- and isoproterenol-induced cardiac hypertrophy in vivo
Creators Name:Freund, C. and Schmidt-Ullrich, R. and Baurand, A. and Dunger, S. and Schneider, W. and Loser, P. and El-Jamali, A. and Dietz, R. and Scheidereit, C. and Bergmann, M.W.
Abstract:Background - In vitro experiments have proposed a role of nuclear factor-κB (NF-κB), a transcription factor, in cardiomyocyte hypertrophy and protection against apoptosis. Currently, the net effect on cardiac remodeling in vivo under common stress stimuli is unclear. Methods and Results - We have generated mice with cardiomyocyte-restricted expression of the NF-κB super-repressor IκBαΔN (ΔN MHC) using the Cre/lox technique. ΔN MHC mice displayed an attenuated hypertrophic response compared with control mice on infusion of angiotensin II (Ang II) or isoproterenol by micro-osmotic pumps, as determined by echocardiography (left ventricular wall dimensions: control plus Ang II, X1.5±0.1 versus sham; ΔN MHC plus Ang II, X1.1±0.1 versus sham; P<0.05; n≥9), heart weight, and histological analysis. Real-time reverse-transcriptase polymerase chain reaction showed significantly reduced expression of hypertrophy markers β-myosin heavy chain and atrial natriuretic peptide in Ang II-treated ΔN MHC mice (P<0.05 versus control plus Ang II; n=4). Neither cardiomyocyte apoptosis nor left ventricular dilatation was observed. In cultured adult rat cardiomyocytes, NF-κB DNA binding activity was increased by both Ang II- and interleukin-6-related cytokines. The latter are known to be released by cardiac fibroblasts on Ang II stimulation and thus could locally increase the NF-κB response of cardiomyocytes. Finally, results from in vitro and in vivo experiments suggest a role for NF-κB in the regulation of prohypertrophic interleukin-6 receptor gp130 on mRNA levels. Conclusions - These results indicate that targeted inhibition of NF-κB in cardiomyocytes in vivo is sufficient to impair Ang II- and isoproterenol-induced hypertrophy without increasing the susceptibility to apoptosis.
Keywords:Angiotensin, Genes, Hypertrophy, Myocytes, Nuclear Factor-κB
Publisher:American Heart Association
Page Range:2319-2325
Date:1 January 2005
Official Publication:https://doi.org/10.1161/01.CIR.0000164237.58200.5A
PubMed:View item in PubMed

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