Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2004-7-9
pubmed: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 naïve (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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0022-2828
pubmed:author
pubmed:issnType
Print
pubmed:volume
37
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
51-61
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:15242735-Active Transport, Cell Nucleus, pubmed-meshheading:15242735-Animals, pubmed-meshheading:15242735-Blotting, Western, pubmed-meshheading:15242735-Cell Nucleus, pubmed-meshheading:15242735-Cytoplasm, pubmed-meshheading:15242735-Cytosol, pubmed-meshheading:15242735-DNA, pubmed-meshheading:15242735-Hemodynamics, pubmed-meshheading:15242735-Homozygote, pubmed-meshheading:15242735-Immunohistochemistry, pubmed-meshheading:15242735-Ischemia, pubmed-meshheading:15242735-Ischemic Preconditioning, Myocardial, pubmed-meshheading:15242735-Mice, pubmed-meshheading:15242735-Mice, Transgenic, pubmed-meshheading:15242735-Myocardial Ischemia, pubmed-meshheading:15242735-Myocardium, pubmed-meshheading:15242735-Myocytes, Cardiac, pubmed-meshheading:15242735-NF-kappa B, pubmed-meshheading:15242735-Proto-Oncogene Proteins c-fos, pubmed-meshheading:15242735-Proto-Oncogene Proteins c-jun, pubmed-meshheading:15242735-Reperfusion Injury, pubmed-meshheading:15242735-Risk, pubmed-meshheading:15242735-Signal Transduction, pubmed-meshheading:15242735-Temperature, pubmed-meshheading:15242735-Time Factors, pubmed-meshheading:15242735-Transcription Factor AP-1, pubmed-meshheading:15242735-Tumor Necrosis Factor-alpha
pubmed:year
2004
pubmed:articleTitle
Tumor necrosis factor-alpha does not modulate ischemia/reperfusion injury in naïve myocardium but is essential for the development of late preconditioning.
pubmed:affiliation
Experimental Research Laboratory, Division of Cardiology, University of Louisville, and the Jewish Hospital Heart and Lung Institute, Louisville, KY 40292, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't