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.