Improved myocardial ischemia/reperfusion injury in mice lacking tumor necrosis factor-alpha.

نویسندگان

  • Naoya Maekawa
  • Hisayasu Wada
  • Tsugiyasu Kanda
  • Tamikazu Niwa
  • Yasuhiro Yamada
  • Kuniaki Saito
  • Hisayoshi Fujiwara
  • Kenji Sekikawa
  • Mitsuru Seishima
چکیده

OBJECTIVES 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.

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عنوان ژورنال:
  • Journal of the American College of Cardiology

دوره 39 7  شماره 

صفحات  -

تاریخ انتشار 2002