2003 Fiscal Year Final Research Report Summary
The role of proinflammatory cytokines in the generation of myocardial ischemia/reperfusion injury
| Project/Area Number |
14570651
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Gifu University |
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Principal Investigator |
WADA Hisayasu Gifu University, Hospital, Assistant Professor, 医学部附属病院, 講師 (10283300)
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| Co-Investigator(Kenkyū-buntansha) |
SEISHIMA Mitsuru Gifu University, School of Medicine, Professor, 医学部, 教授 (10171315)
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| Project Period (FY) |
2002 – 2003
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| Keywords | ischemia / reperfusion injury / knockout mice / transgenic mice / TNF-α / NE-κB / inflammatory cell infiltration / cell adhesion molecules / chemokines |
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| Research Abstract |
Proinflammatory cytokines, especially tumor necrosis factor-α (TNF-α) are thought to be involved in the pathogenesis of myocardial ischemia/reperfusion (I/R) injury. However, their precise role in I/R injury is still unknown. The heart was exposed by left lateral thoracotomy and the left coronary artery was occluded for 30 minutes, then reperfused for 120 minutes in TNF-α knockout (KO) and wild-type (WT) mice. The infarct size in TNF-α KO 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 compared with those in WT. The activation of NE-κB, the expressions of chemokines and adhesion molecules, and the infiltration of leukocytes were also significantly reduced in TNF-α KO compared with WT. These findings provide evidence that TNF-α aggravates I/R injury. TNF-α exacerbates myocardial I/R injury at an early stage of reperfusion by activating NE-κB, thereby inducing chemokines and adhesion molecules, and facilitating leukocyte infiltration. However, after permanent coronary occlusion, infarct size was slightly but significantly smaller in WT mice than TNF-α KO mice. WT and TNF-α KO mice were irradiated and the bone marrow cells from GFP transgenic mice were transplanted. After I/R, GFP positive cells were detected in the infarct area and the number of GEP positive cells was significantly increased in TNF-α KO mice than WT mice.
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