15142841

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4

In the present study, we examined whether NF-kappaB activation is required for cardiac hypertrophy in vivo. Cardiac hypertrophy in rats was induced by aortic banding for 1, 3, and 5 days and 1-6 wk, and age-matched sham-operated rats served as controls. In a separate group of rats, an IkappaB-alpha dominant negative mutant (IkappaB-alphaM), a superrepressor of NF-kappaB activation, or pyrrolidinedithiocarbamate (PDTC), an antioxidant that can inhibit NF-kappaB activation, was administered to aortic-banded rats for 3 wk. The heart weight-to-body weight ratio was significantly increased at 5 days after aortic banding, peaked at 4 wk, and remained elevated at 6 wk compared with age-matched sham controls. Atrial natriuretic peptide and brain natriuretic peptide mRNA expressions were significantly increased after 1 wk of aortic banding, reached a maximum between 2 and 3 wk, and remained increased at 6 wk compared with age-matched sham controls. NF-kappaB activity was significantly increased at 1 day, reached a peak at 3 wk, and remained elevated at 6 wk, and IKK-beta activity was significantly increased at 1 day, peaked at 5 days, and then decreased but remained elevated at 6 wk after aortic banding compared with age-matched sham controls. Inhibiting NF-kappaB activation in vivo by cardiac transfection of IkappaB-alphaM or by PDTC treatment significantly attenuated the development of cardiac hypertrophy in vivo with a concomitant decrease in NF-kappaB activity. Our results suggest that NF-kappaB activation is required for the development of cardiac hypertrophy in vivo and that NF-kappaB could be an important target for inhibiting the development of cardiac hypertrophy in vivo.

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0363-6135

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H1712-20

pubmed-meshheading:15142841-Adenoviridae, pubmed-meshheading:15142841-Animals, pubmed-meshheading:15142841-Antioxidants, pubmed-meshheading:15142841-Aorta, pubmed-meshheading:15142841-Atrial Natriuretic Factor, pubmed-meshheading:15142841-Cardiomegaly, pubmed-meshheading:15142841-I-kappa B Kinase, pubmed-meshheading:15142841-I-kappa B Proteins, pubmed-meshheading:15142841-Ligation, pubmed-meshheading:15142841-Male, pubmed-meshheading:15142841-Myocardium, pubmed-meshheading:15142841-NF-kappa B, pubmed-meshheading:15142841-Natriuretic Peptide, Brain, pubmed-meshheading:15142841-Proline, pubmed-meshheading:15142841-Protein-Serine-Threonine Kinases, pubmed-meshheading:15142841-RNA, Messenger, pubmed-meshheading:15142841-Rats, pubmed-meshheading:15142841-Rats, Sprague-Dawley, pubmed-meshheading:15142841-Signal Transduction, pubmed-meshheading:15142841-Thiocarbamates, pubmed-meshheading:15142841-Transfection

NF-kappaB activation is required for the development of cardiac hypertrophy in vivo.

Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't