Activation of nuclear factor-kappaB and its proinflammatory mediator cascade in the infarcted rat heart.
Nuclear transcription factor (NF)-kappaB regulates inflammatory and immune responses by increasing the expression of specific inflammatory genes in various tissues. Whether the infarcted heart includes the activation of NF-kappaB and a proinflammatory mediator cascade that it regulates has not been fully explored. Herein, we monitored the temporal and spatial activation of NF-kappaB, together with expression of tumor necrosis factor (TNF)-alpha, vascular cell adhesion molecule-1 (VCAM-1), and transforming growth factor (TGF)-beta(1), in the infarcted rat heart at and remote to MI from day 3 to day 28 following left coronary artery ligation. Compared to the normal heart, we observed NF-kappaB activation, together with the elevated expression of VCAM-1 in endothelial cells, TNF-alpha and TGF-beta(1) in inflammatory cells at sites of repair in the infarcted heart, which started on day 3, peaked on day 7, and gradually declined thereafter. Our findings suggest NF-kappaB activation and its proinflammatory mediator cascade are contributory to the inflammatory response and remodeling that appear at various sites of repair in the infarcted rat heart.
Lu
Li
L
Division of Cardiovascular Diseases, Department of Medicine, University of Tennessee, Health Science Center, Memphis, TN, USA.
Chen
Sue S
SS
Zhang
John Q
JQ
Ramires
Felix J
FJ
Sun
Yao
Y
D000818:Animals; D015870:Gene Expression; D017403:In Situ Hybridization; D018836:Inflammation Mediators / Q000378:metabolism*; D008297:Male; D009203:Myocardial Infarction / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000235:genetics; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics
D018836:Inflammation Mediators; D016328:NF-kappa B; D012333:RNA, Messenger; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1