Tissue-Specific Effects of the Nuclear Factor κB Subunit p50 on Myocardial Ischemia-Reperfusion Injury

Abstract

Nuclear factor B (NF-B) is a ubiquitous transcription factor activated by various stimuli implicated in ischemia-reperfusion injury. However, the role of NF-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-B subunit p50. Electrophoretic mobility shift assays validated NF-B 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 ischemiareperfusion injury, transplantation of WT bone marrow in KO animals abolished it. Thus, deletion of the NF-B subunit p50 reduces ischemia-reperfusion injury in vivo, associated with less neutrophil infiltration. Bone marrow transplantation experiments indicate that impaired NF-B activation in p50 KO leukocytes attenuates cardiac damage.

The IκB Kinase β/Nuclear Factor κB Signaling Pathway Protects the Heart From Hemodynamic Stress Mediated by the Regulation of Manganese Superoxide Dismutase Expression

“…In addition, Frantz et al also reported that the reduction of cardiac ischemia/reperfusion injury in p50-deficient mice was abolished with transplantation of bone marrow cells isolated from wild-type mice, indicating that the primary mechanism of injury is activation of NF-B in infiltrating leukocytes and not in cardiomyocytes. 22 Taken together, these observations suggest that p50-deficient mice may not be the appropriate model to clarify the role of the NF-B pathway in cardiomyocytes. Thus, we used cardiomyocyte-specific IKK␤-deficient mice in this study.…”

Efecto del ejercicio agudo sobre la expresión del receptor tipo Toll-4 y los mecanismos inflamatorios en corazón de rata

“…Esta mayor traslocación del factor de transcripción fue coincidente con el aumento de la subunidad p50 en núcleos y con la expresión incrementada del ARNm de iNOS. También es importante destacar que está ampliamente demostrado que el incremento de la síntesis de óxido nítrico, produce peroxinitrito, un radical que se ha postulado como uno de los mayores responsables en la muerte celular en este tipo de tejido esquelético 33 . En todas estas investigaciones además se pone de manifiesto que un aumento en los niveles de inflamación incrementa el daño celular en el tejido cardiaco.…”

Effects of stent implementation on plasma levels of asymmetric dimethylarginine in patients with or without ST-segment elevation acute myocardial infarction

“…The severity of myocardial damage is related to the degree of infection (25,26). Pharmacological inhibition or targeted deletion of elements of inflammatory mediators has been proven to be effective in reducing infarction, improving myocardial function and survival (27)(28)(29)(30). Pro-inflammatory cytokines are known to stimulate the formation of reactive oxygen species, which in turn amplify the inflammatory processes.…”