Warning: Undefined variable $zfal in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 525
Deprecated: str_replace(): Passing null to parameter #3 ($subject) of type array|string is deprecated in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 525
Warning: Undefined variable $sterm in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 530
free
Warning: Undefined variable $sterm in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 531
free free
English Wikipedia
Nephropedia Template TP (
Twit Text
DeepDyve Pubget Overpricing |
lüll Cardiomyocyte NF-kappaB p65 promotes adverse remodelling, apoptosis, and endoplasmic reticulum stress in heart failure Hamid T; Guo SZ; Kingery JR; Xiang X; Dawn B; Prabhu SDCardiovasc Res 2011[Jan]; 89 (1): 129-38AIMS: the role of nuclear factor (NF)-kappaB in heart failure (HF) is not well defined. We sought to determine whether myocyte-localized NF-kappaB 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 kappaBalpha (IkappaBalpha(S32A,S36A)) underwent coronary ligation (to induce HF) or sham operation. Over 4 weeks, the remote myocardium of ligated hearts exhibited robust NF-kappaB 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, increased apoptosis, down-regulation of ER protein chaperones, and up-regulation of the ER stress-activated pro-apoptotic factor CHOP. Compared with NTg HF, Tg-IkappaBalpha(S32A,S36A) HF mice exhibited: (i) improved survival, chamber remodelling, systolic function, and pulmonary congestion, (ii) markedly diminished NF-kappaB p65 activation, cytokine expression, and fibrosis, and (iii) a three-fold reduction in apoptosis. Moreover, Tg-IkappaBalpha(S32A,S36A) HF hearts exhibited maintained expression of ER chaperones and CHOP when compared with sham. In cardiomyocytes, NF-kappaB activation was required for ER stress-mediated apoptosis, whereas abrogation of myocyte NF-kappaB shifted the ER stress response to one of adaptation and survival. CONCLUSION: persistent myocyte NF-kappaB p65 activation in HF exacerbates cardiac remodelling by imparting pro-inflammatory, pro-fibrotic, and pro-apoptotic effects. p65 modulation of cell death in HF may occur in part from NF-kappaB-mediated transformation of the ER stress response from one of adaptation to one of apoptosis.|Animals[MESH]|Apoptosis/physiology[MESH]|Cell Line[MESH]|Cytokines/genetics[MESH]|Endoplasmic Reticulum/physiology[MESH]|Fibrosis[MESH]|Heart Failure/genetics/*pathology/*physiopathology[MESH]|Humans[MESH]|I-kappa B Proteins/antagonists & inhibitors/genetics/physiology[MESH]|In Vitro Techniques[MESH]|Inflammation Mediators/physiology[MESH]|Male[MESH]|Mice[MESH]|Mice, Inbred C57BL[MESH]|Mice, Transgenic[MESH]|Mutant Proteins/genetics/metabolism[MESH]|Myocardial Infarction/pathology/physiopathology[MESH]|Myocytes, Cardiac/pathology/*physiology[MESH]|NF-KappaB Inhibitor alpha[MESH]|Stress, Physiological[MESH]|Transcription Factor RelA/*physiology[MESH]|Ventricular Remodeling/genetics/physiology[MESH] |