title: Improved myocardial ischemia/reperfusion injury in mice lacking tumor necrosis factor-alpha.
abstract: OBJECTIVE
  This study sought to assess the role of tumor necrosis factor-alpha (TNF-alpha) in myocardial ischemia/reperfusion (I/R) injury using TNF-alpha knockout (KO) mice.
  
  
  BACKGROUND
  Tumor necrosis factor-alpha is thought to be involved in the pathogenesis of myocardial I/R injury by promoting leukocyte infiltration of the myocardium. However, the precise role of TNF-alpha in I/R injury is still unknown.
  
  
  METHODS
  The hearts in TNF-alpha KO and wild-type (WT) mice were exposed by left lateral thoracotomy, and the left coronary artery was occluded for 30 min then reperfused for 120 min.
  
  
  RESULTS
  The infarct size in TNF-alpha KO mice was significantly reduced compared with WT mice. The frequency of arrhythmia was decreased, and cardiac function during reperfusion was significantly improved in TNF-alpha KO mice compared with WT mice. The activation of nuclear factor-kappaB (NF-kappaB), the expression of chemokines and adhesion molecules and the infiltration of leukocytes were also significantly reduced in TNF-alpha KO mice, compared with WT mice. These findings provide evidence that TNF-alpha aggravates I/R injury.
  
  
  CONCLUSIONS
  Tumor necrosis factor-alpha exacerbates myocardial I/R injury at an early stage of reperfusion by activating NF-kappaB, thereby inducing chemokines and adhesion molecules and facilitating leukocyte infiltration.
authors.affiliation: Department of Laboratory Medicine, Gifu University School of Medicine, Gifu, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Maekawa
authors.forename: Hisayasu
authors.initials: H
authors.lastname: Wada
authors.forename: Tsugiyasu
authors.initials: T
authors.lastname: Kanda
authors.forename: Tamikazu
authors.initials: T
authors.lastname: Niwa
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yamada
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Saito
authors.forename: Hisayoshi
authors.initials: H
authors.lastname: Fujiwara
authors.forename: Kenji
authors.initials: K
authors.lastname: Sekikawa
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Seishima
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D020556:Neutrophil Infiltration; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency / Q000502:physiology*
chemical_list: D015815:Cell Adhesion Molecules; D018925:Chemokines; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha