| First Author | Frantz S | Year | 2007 |
| Journal | Am J Pathol | Volume | 171 |
| Issue | 2 | Pages | 507-12 |
| PubMed ID | 17556593 | Mgi Jnum | J:143829 |
| Mgi Id | MGI:3829134 | Doi | 10.2353/ajpath.2007.061042 |
| Citation | Frantz S, et al. (2007) Tissue-specific effects of the nuclear factor kappaB subunit p50 on myocardial ischemia-reperfusion injury. Am J Pathol 171(2):507-12 |
| abstractText | Nuclear factor kappaB (NF-kappaB) is a ubiquitous transcription factor activated by various stimuli implicated in ischemia-reperfusion injury. However, the role of NF-kappaB in cardiac ischemia-reperfusion injury has not yet been well defined. Therefore, we investigated reperfusion damage in mice with targeted deletion of the NF-kappaB subunit p50. Electrophoretic mobility shift assays validated NF-kappaB 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-kappaB subunit p50 reduces ischemia-reperfusion injury in vivo, associated with less neutrophil infiltration. Bone marrow transplantation experiments indicate that impaired NF-kappaB activation in p50 KO leukocytes attenuates cardiac damage. |
