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

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

Research output: Contribution to journalArticlepeer-review

165 Citations (Scopus)


OBJECTIVES: This study sought to assess the role of tumor necrosis factor-α (TNF-α) in myocardial ischemia/reperfusion (I/R) injury using TNF-α knockout (KO) mice. BACKGROUND: Tumor necrosis factor-α 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-α in I/R injury is still unknown. METHODS: The hearts in TNF-α 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-α 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-α KO mice compared with WT mice. The activation of nuclear factor-κB (NF-κB), the expression of chemokines and adhesion molecules and the infiltration of leukocytes were also significantly reduced in TNF-α KO mice, compared with WT mice. These findings provide evidence that TNF-α aggravates I/R injury. CONCLUSIONS: Tumor necrosis factor-α exacerbates myocardial I/R injury at an early stage of reperfusion by activating NF-κB, thereby inducing chemokines and adhesion molecules and facilitating leukocyte infiltration.

Original languageEnglish
Pages (from-to)1229-1235
Number of pages7
JournalJournal of the American College of Cardiology
Issue number7
Publication statusPublished - 03-04-2002
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine


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