Tumor necrosis factor-alpha contributes to ischemia- and reperfusion-induced endothelial activation in isolated hearts

Citation
C. Kupatt et al., Tumor necrosis factor-alpha contributes to ischemia- and reperfusion-induced endothelial activation in isolated hearts, CIRCUL RES, 84(4), 1999, pp. 392-400
Citations number
41
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cardiovascular & Hematology Research
Journal title
CIRCULATION RESEARCH
ISSN journal
0009-7330 → ACNP
Volume
84
Issue
4
Year of publication
1999
Pages
392 - 400
Database
ISI
SICI code
0009-7330(19990305)84:4<392:TNFCTI>2.0.ZU;2-S
Abstract
During myocardial reperfusion, polymorphonuclear neutrophil (PMN) adhesion involving the intercellular adhesion molecule-1 (ICAM-1) may lead to aggrav ation and prolongation of reperfusion injury. We studied the role of early tumor necrosis factor-alpha (TNF-alpha) cleavage and nuclear factor-kappa B (NF-kappa B) activation on ICAM-1 expression and venular adhesion of PMN i n isolated hearts after ischemia (15 minutes) and reperfusion (30 to 480 mi nutes). NF-kappa B activation (electromobility shift assay) was found after 30 minutes of reperfusion and up to 240 minutes. ICAM-1 mRNA, assessed by Northern blot, increased during the same interval. Functional effect of new ly synthesized adhesion molecules was found by quantification (in situ fluo rescence microscopy) of PMN, given as bolus after ischemia, which became ad herent to small coronary venules (10 to 50 mu m in diameter). After 480 min utes of reperfusion, ICAM-1-dependent PMN adhesion increased 2.5-fold compa red with PMN adhesion obtained during acute reperfusion. To study the influ ence of NF-kappa B on PMN adhesion, we inhibited NF-kappa B activation by t ransfection of NF-kappa B decoy oligonucleotides into isolated hearts using HJV-liposomes. Decoy NF-kappa B but not control oligonucleotides blocked I CAM-1 upregulation and inhibited the subacute increase in PMN adhesion. Sim ilar effects were obtained using BB 1101 (10 mu g), an inhibitor of TNF-alp ha cleavage enzyme. These data suggest that ischemia and reperfusion in iso lated hearts cause liberation of TNF-alpha, activation of NF-kappa B, and u pregulation of ICAM-1, an adhesion molecule involved in inflammatory respon se after ischemia and reperfusion.