| First Author | Freund C | Year | 2005 |
| Journal | Circulation | Volume | 111 |
| Issue | 18 | Pages | 2319-25 |
| PubMed ID | 15870116 | Mgi Jnum | J:111645 |
| Mgi Id | MGI:3654611 | Doi | 10.1161/01.CIR.0000164237.58200.5A |
| Citation | Freund C, et al. (2005) Requirement of nuclear factor-kappaB in angiotensin II- and isoproterenol-induced cardiac hypertrophy in vivo. Circulation 111(18):2319-25 |
| abstractText | BACKGROUND: In vitro experiments have proposed a role of nuclear factor-kappaB (NF-kappaB), 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-kappaB super-repressor IkappaBalphaDeltaN (DeltaN(MHC)) using the Cre/lox technique. DeltaN(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; DeltaN(MHC) plus Ang II, x1.1+/-0.1 versus sham; P<0.05; n> or =9), heart weight, and histological analysis. Real-time reverse-transcriptase polymerase chain reaction showed significantly reduced expression of hypertrophy markers beta-myosin heavy chain and atrial natriuretic peptide in Ang II-treated DeltaN(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-kappaB 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-kappaB response of cardiomyocytes. Finally, results from in vitro and in vivo experiments suggest a role for NF-kappaB in the regulation of prohypertrophic interleukin-6 receptor gp130 on mRNA levels. CONCLUSIONS: These results indicate that targeted inhibition of NF-kappaB in cardiomyocytes in vivo is sufficient to impair Ang II- and isoproterenol-induced hypertrophy without increasing the susceptibility to apoptosis. |
