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This Article Full Text Full Text (PDF) All Versions of this Article: 291/3/H1337    most recent 01175.2005v2 01175.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (23) Citing Articles via Google Scholar Google Scholar Articles by Kawano, S. Articles by Sunagawa, K. Search for Related Content PubMed PubMed Citation Articles by Kawano, S. Articles by Sunagawa, K.

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

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

Submitted 6 November 2005 ; accepted in final form 12 April 2006

NF-B is a key transcription factor that regulates inflammatory processes. In the present study, we tested the hypothesis that blockade of NF-B ameliorates cardiac remodeling and failure after myocardial infarction (MI). Knockout mice with targeted disruption of the p50 subunit of NF-B (KO) were used to block the activation of NF-B. MI was induced by ligation of the left coronary artery in male KO and age-matched wild-type (WT) mice. NF-B was activated in noninfarct as well as infarct myocardium in WT + MI mice, while the activity was completely abolished in KO mice. Blockade of NF-B significantly reduced early ventricular rupture after MI and improved survival by ameliorating congestive heart failure. Echocardiographic and pressure measurements revealed that left ventricular fractional shortening and maximum rate of rise of left ventricular pressure were significantly increased and end-diastolic pressure was significantly decreased in KO + MI mice compared with WT + MI mice. Histological analysis demonstrated significant suppression of myocyte hypertrophy as well as interstitial fibrosis in the noninfarct myocardium of KO + MI mice. Blockade of NF-B did not ameliorate expression of proinflammatory cytokines in infarct or noninfarct myocardium. In contrast, phosphorylation of c-Jun NH₂-terminal kinase was almost completely abolished in KO + MI mice. The present study demonstrates that targeted disruption of the p50 subunit of NF-B reduces ventricular rupture as well as improves cardiac function and survival after MI. Blockade of NF-B might be a new therapeutic strategy to attenuate cardiac remodeling and failure after MI.

cardiac remodeling; inflammation; mitogen-activated protein kinases

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