Signal transduction through nuclear factor kappa B in ischemia-reperfusion and heart failure

Abstract.

Ischemic heart disease is the major cause of morbity and mortality in the Western world, with chronic heart failure as one complication. Ischemia-reperfusion injury may induce cardiomyocyte cell death by necrosis or apoptosis. The heart can be adapted to tolerate an ischemic event by preceeding brief episodes of ischemia and reperfusion, called preconditioning. Innate immunity has the latest years surfaced as important for the development of cardiovascular pathology as well as for myocardial protection. Nuclear factor kappa B (NFκB) is a redox sensitive transcription factor which contributes to the regulation of innate and adaptive immunity. NFκB regulates a battery of inflammatory genes, and has been indicated to play a role in the development of numerous pathological states. Activation of NFκB induces gene programs leading to transcription of factors which promote inflammation, among them leukocyte adhesion molecules, cytokines such as tumor necrosis factor alpha, and chemokines, but may in some situations also promote tissue remodelling, the resolution of inflammation, and transcription of some few substances with possible antiinflammatory effects. The present paper reviews the basic regulation of NFκB, and the possible role of NFκB activation in ischemia-reperfusion injury, in adaptation to ischemia-reperfusion injury, and in chronic heart failure.