AJP - Heart Track the topics, authors and articles important to you
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
 QUICK SEARCH:   [advanced]


     


Am J Physiol Heart Circ Physiol (April 21, 2006). doi:10.1152/ajpheart.01175.2005
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
291/3/H1337    most recent
01175.2005v2
01175.2005v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kawano, S.
Right arrow Articles by Sunagawa, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kawano, S.
Right arrow Articles by Sunagawa, K.
Submitted on November 6, 2005
Accepted on April 12, 2006

Blockade of NF-{kappa}B improves cardiac function and survival after myocardial infarction

Shunichi Kawano1, Toru Kubota1*, Yoshiya Monden1, Takaki Tsutsumi1, Takahiro Inoue1, Natsumi Kawamura1, Hiroyuki Tsutsui2, and Kenji Sunagawa1

1 Kyushu University Graduate School of Medical Sciences, Department of Cardiovascular Medicine, Fukuoka, Japan
2 Hokkaido University Graduate School of Medicine, Department of Cardiovascular Medicine, Sapporo, Japan

* To whom correspondence should be addressed. E-mail: kubotat{at}cardiol.med.kyushu-u.ac.jp.

NF-{kappa}B is a key transcription factor that regulates inflammatory processes. In the present study, we tested the hypothesis that blockade of NF-{kappa}B ameliorate cardiac remodeling and failure after myocardial infarction (MI). Knock-out mice with targeted disruption of the p50 subunit of NF-{kappa}B (KO) were used to block the activation of NF-{kappa}B. MI was induced by ligation of the left coronary artery in male KO and age-matched wild-type (WT) mice. NF-{kappa}B was activated in non-infarct as well as infarct myocardium in WT+MI mice, while the activity was completely abolished in KO mice. Blockade of NF-{kappa}B significantly reduced early ventricular rupture after MI and improved the survival by ameliorating congestive heart failure. Echocardiographic and pressure measurement revealed that left ventricular fractional shortening and + dP/dtmax were significantly increased and end-diastolic pressure was significantly decreased in KO+MI mice compared to WT+MI mice. Histological analysis demonstrated significant suppression of myocyte hypertrophy as well as interstitial fibrosis in non-infarct myocardium in KO+MI mice. Blockade of NF-{kappa}B did not ameliorate expression of proinflammatory cytokines in infarct or non-infarct myocardium. In contrast, phosphorylation of c-Jun N-terminal kinase was almost completely abolished in KO+MI mice. The present study demonstrates that targeted disruption of the p50 subunit of NF-{kappa}B reduces ventricular rupture as well as improves cardiac function and survival after MI. Blockade of NF-{kappa}B might be a new therapeutic strategy to attenuate cardiac remodeling and failure after MI.







HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Visit Other APS Journals Online
Copyright © 1977 by the American Physiological Society.