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

Frantz, S; Tillmanns, J; Kuhlencordt, PJ; Schmidt, I; Adamek, A; Dienesch, C; Thum, T; Gerondakis, S; Ertl, G; Bauersachs, J

Author(s): Frantz, S; Tillmanns, J; Kuhlencordt, PJ; Schmidt, I; Adamek, A; Dienesch, C; Thum, T; Gerondakis, S; Ertl, G; Bauersachs, J;
Details: Publication Year 2007-08,Volume 171,Issue #2,Page 507-512
Journal Title: AMERICAN JOURNAL OF PATHOLOGY
Publication Type: Journal Article
Abstract: Nuclear factor KB (NF-kappa B) is a ubiquitous transcription factor activated by various stimuli implicated in ischemia-reperfusion injury. However, the role of NF-kappa B in cardiac ischemia-reperfusion injury has not yet been well defined. Therefore, we investigated reperfusion damage in mice with targeted deletion of the NF-KB subunit p50. Electrophoretic mobility shift assays validated NF-KB activation in wild-type (wi) 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-kappa B subunit p50 reduces ischemia-reperfusion injury in vivo, associated with less neutrophil infiltration. Bone marrow transplantation experiments indicate that impaired NF-KB activation in P50 KO leukocytes attenuates cardiac damage.
Publisher: AMER SOC INVESTIGATIVE PATHOLOGY, INC
Keywords: CARDIAC MYOCYTES; ISCHEMIA/REPERFUSION INJURY; EMBRYONIC LETHALITY; LIVER DEGENERATION; DEFICIENT MICE; MOUSE MODEL; ACTIVATION; INFARCTION; INFLAMMATION; INHIBITION
Publisher's Version: https://doi.org/10.2353/ajpath.2007.061042
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2007-08-01 12:00:00