Tissue-specific effects of the nuclear factor κB subunit p50 on myocardial ischemia-reperfusion injury

Stefan Frantz, Jochen Tillmanns, Peter J. Kuhlencordt, Isabel Schmidt, Anna Adamek, Charlotte Dienesch, Thomas Thum, Steve Gerondakis, Georg Ertl, Johann Bauersachs

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63 Citations (Scopus)


Nuclear factor κB (NF-κB) is a ubiquitous transcription factor activated by various stimuli implicated in ischemia-reperfusion injury. However, the role of NF-κB in cardiac ischemia-reperfusion injury has not yet been well defined. Therefore, we investigated reperfusion damage in mice with targeted deletion of the NF-κB subunit p50. Electrophoretic mobility shift assays validated NF-κB activation in wild-type (WT) but not p50 knockout (KO) mice. KO and WT animals underwent 30 minutes of coronary artery ligation and 24 hours of reperfusion in vivo. Ischemia-reperfusion damage was significantly reduced in the p50 KO when compared with matching WT mice. Although adhesion molecules such as intercellular adhesion molecule were up-regulated in left ventricles of p50 KO animals, fewer neutrophils infiltrated the infarct area, suggesting leukocytes as a potential mediator of the protection observed in the p50 KO. This was confirmed in adoptive transfer experiments: whereas transplantation of KO bone marrow in KO animals sustained the protective effect on ischemia-reperfusion injury, transplantation of WT bone marrow in KO animals abolished it Thus, deletion of the NF-κB subunit p50 reduces ischemia-reperfusion injury in vivo, associated with less neutrophil infiltration. Bone marrow transplantation experiments indicate that impaired NF-κB activation in p50 KO leukocytes attenuates cardiac damage.

Original languageEnglish
Pages (from-to)507-512
Number of pages6
JournalAmerican Journal of Pathology
Issue number2
Publication statusPublished - 1 Jan 2007
Externally publishedYes

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