NF-κB activation is required for adaptive cardiac hypertrophy

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Item Type:	Article
Title:	NF-κB activation is required for adaptive cardiac hypertrophy
Creators Name:	Zelarayan, L., Renger, A., Noack, C., Zafiriou, M.P., Gehrke, C., van der Nagel, R., Dietz, R., de Windt, L. and Bergmann, M.W.
Abstract:	AIMS: We have previously shown that cardiac-specific inhibition of NF-{kappa}B attenuates Angiotensin II (AngII) induced left ventricular (LV) hypertrophy in vivo. We now tested whether NF-{kappa}B inhibition is able to block LV-remodeling upon chronic pressure overload and chronic AngII-stimulation. METHODS: Cardiac-restricted NF-{kappa}B inhibition was achieved by expression of a stabilized I{kappa}B{alpha} mutant (I{kappa}B{alpha}DeltaN) in cells with an active {alpha}MHC promoter employing the Cre/lox technique. Upon low gradient trans -aortic constriction (TAC, gradient 21+/-3 mmHg), hypertrophy was induced in both male and female control mice after 4 weeks. RESULTS: At this time, LV-hypertrophy was blocked in transgenic male but not female mice with NF-{kappa}B inhibition. Amelioration of LV-hypertrophy was associated with activation of NF-{kappa}B by dihydrotestosterone in isolated neonatal cardiomyocytes. LV remodeling was not attenuated by NF-{kappa}B inhibition after 8 weeks TAC, demonstrated by decreased fractional shortening (FS) in both control and TG mice irrespective of gender. Similar results were obtained, when TAC was performed with higher gradients (48+/-4mmHG): In TG mice FS dropped to similar low levels over the same time course (FS sham: 29+/-1% (mean+/-SEM), FS control+14days TAC: 13+/-3%, FS TG+14days TAC: 9+/-5%). Similarly, LV remodeling was accelerated by NF-{kappa}B inhibition in an AngII-dependent genetic heart failure model (AT1-R({alpha}MHC)) associated with significantly increased cardiac fibrosis in double AT1-R({alpha}MHC)/TG mice. CONCLUSIONS: NF-{kappa}B inhibition attenuates cardiac hypertrophy in a gender specific manner but does not alter the course of stress-induced LV remodeling indicating NF-{kappa}B to be required for adaptive cardiac hypertrophy.
Keywords:	NF-{kappa}B, Hypertrophy, Remodelling, Signal Transduction, Apoptosis, Fibrosis, Angiotensin, Hypertension, Animals, Mice
Source:	Cardiovascular Research
ISSN:	0008-6363
Publisher:	Oxford University Press
Volume:	84
Number:	3
Page Range:	416-424
Date:	1 December 2009
Official Publication:	https://doi.org/10.1093/cvr/cvp237
PubMed:	View item in PubMed

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