Cardiomyocyte NF-κB p65 promotes adverse remodelling, apoptosis, and endoplasmic reticulum stress in heart failure.

ABSTRACT:

Aims

the role of nuclear factor (NF)-κB in heart failure (HF) is not well defined. We sought to determine whether myocyte-localized NF-κB p65 activation in HF exacerbates post-infarction remodelling and promotes maladaptive endoplasmic reticulum (ER) stress.

Methods and results

non-transgenic (NTg) and transgenic (Tg) mice with myocyte-restricted overexpression of a phosphorylation-resistant inhibitor of κBα (IκBα(S32A,S36A)) underwent coronary ligation (to induce HF) or sham operation. Over 4 weeks, the remote myocardium of ligated hearts exhibited robust NF-κB activation that was almost exclusively p65 beyond 24 h. Compared with sham at 4 weeks, NTg HF hearts were dilated and dysfunctional, and exhibited hypertrophy, fibrosis, up-regulation of inflammatory cytokines, incre

SUBMITTER: Hamid T 

PROVIDER: S-EPMC3002872 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature