| First Author | Maekawa N | Year | 2002 |
| Journal | J Am Coll Cardiol | Volume | 39 |
| Issue | 7 | Pages | 1229-35 |
| PubMed ID | 11923051 | Mgi Jnum | J:106180 |
| Mgi Id | MGI:3617712 | Doi | 10.1016/s0735-1097(02)01738-2 |
| Citation | Maekawa N, et al. (2002) Improved myocardial ischemia/reperfusion injury in mice lacking tumor necrosis factor-alpha. J Am Coll Cardiol 39(7):1229-35 |
| abstractText | 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. |
