| First Author | Dawn B | Year | 2004 |
| Journal | J Mol Cell Cardiol | Volume | 37 |
| Issue | 1 | Pages | 51-61 |
| PubMed ID | 15242735 | Mgi Jnum | J:132469 |
| Mgi Id | MGI:3775997 | Doi | 10.1016/j.yjmcc.2004.03.012 |
| Citation | Dawn B, et al. (2004) Tumor necrosis factor-alpha does not modulate ischemia/reperfusion injury in naive myocardium but is essential for the development of late preconditioning. J Mol Cell Cardiol 37(1):51-61 |
| abstractText | The role of tumor necrosis factor (TNF)-alpha in myocardial ischemia/reperfusion injury remains controversial. We used homozygous TNF-alpha null mice (TNF-alpha(-/-)) to determine whether TNF-alpha modulates myocardial ischemia/reperfusion injury. Mice were subjected to a 30-min coronary occlusion followed by 24 h of reperfusion. When wild-type mice were preconditioned with six cycles of 4-min coronary occlusion/4-min reperfusion 24 h before the 30-min occlusion, infarct size was reduced from 58.6 +/- 1.9% of the risk region to 19.3 +/- 3.6%, indicating a late preconditioning (PC) effect. In non-preconditioned TNF-alpha(-/-) mice, infarct size was similar to that observed in wild-type mice (55.5 +/- 3.7%). However, in TNF-alpha(-/-) mice preconditioned with six occlusion/reperfusion cycles 24 h earlier, infarct size was not reduced (55.2 +/- 5.7%), indicating that the late PC protection against infarction was completely abolished. While minimal TNF-alpha immunoreactivity was detected in sham-operated hearts, extensive TNF-alpha expression was noted in the cytoplasm of cardiomyocytes in the ischemic/reperfused region 30 min after the PC ischemia. At 30 min after PC, wild-type mice exhibited increased DNA-binding activity of nuclear factor-kappa B (NF-kappa B) and activator protein-1 (AP-1) and nuclear translocation of p65, c-Jun and c-Fos; all of these changes were absent in TNF-alpha(-/-) mice. These data demonstrate that TNF-alpha does not modulate infarct size in the naive (non-preconditioned) state but is essential for the development of the late phase of ischemic PC, possibly via the activation of NF-kappa B and AP-1 transcription factors. |
