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 journalArticle

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Abstract

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
Volume39
Issue number7
DOIs
Publication statusPublished - 03-04-2002
Externally publishedYes

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Myocardial Reperfusion Injury
Reperfusion Injury
Myocardial Ischemia
Tumor Necrosis Factor-alpha
Knockout Mice
Cell Adhesion Molecules
Chemokines
Reperfusion
Thoracotomy
Cardiac Arrhythmias
Coronary Vessels
Myocardium
Leukocytes

All Science Journal Classification (ASJC) codes

  • Nursing(all)

Cite this

Maekawa, Naoya ; Wada, Hisayasu ; Kanda, Tsugiyasu ; Niwa, Tamikazu ; Yamada, Yasuhiro ; Saito, Kuniaki ; Fujiwara, Hisayoshi ; Sekikawa, Kenji ; Seishima, Mitsuru. / Improved myocardial ischemia/reperfusion injury in mice lacking tumor necrosis factor-α. In: Journal of the American College of Cardiology. 2002 ; Vol. 39, No. 7. pp. 1229-1235.
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abstract = "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.",
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Maekawa, N, Wada, H, Kanda, T, Niwa, T, Yamada, Y, Saito, K, Fujiwara, H, Sekikawa, K & Seishima, M 2002, 'Improved myocardial ischemia/reperfusion injury in mice lacking tumor necrosis factor-α', Journal of the American College of Cardiology, vol. 39, no. 7, pp. 1229-1235. https://doi.org/10.1016/S0735-1097(02)01738-2

Improved myocardial ischemia/reperfusion injury in mice lacking tumor necrosis factor-α. / Maekawa, Naoya; Wada, Hisayasu; Kanda, Tsugiyasu; Niwa, Tamikazu; Yamada, Yasuhiro; Saito, Kuniaki; Fujiwara, Hisayoshi; Sekikawa, Kenji; Seishima, Mitsuru.

In: Journal of the American College of Cardiology, Vol. 39, No. 7, 03.04.2002, p. 1229-1235.

Research output: Contribution to journalArticle

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T1 - Improved myocardial ischemia/reperfusion injury in mice lacking tumor necrosis factor-α

AU - Maekawa, Naoya

AU - Wada, Hisayasu

AU - Kanda, Tsugiyasu

AU - Niwa, Tamikazu

AU - Yamada, Yasuhiro

AU - Saito, Kuniaki

AU - Fujiwara, Hisayoshi

AU - Sekikawa, Kenji

AU - Seishima, Mitsuru

PY - 2002/4/3

Y1 - 2002/4/3

N2 - 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.

AB - 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.

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