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

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 (NFkappaB) is a redox sensitive transcription factor which contributes to the regulation of innate and adaptive immunity. NFkappaB regulates a battery of inammatory genes, and has been indicated to play a role in the development of numerous pathological states. Activation of NFkappaB induces gene programs leading to transcription of factors which promote inammation, 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 inammation, and transcription of some few substances with possible antiinammatory effects. The present paper reviews the basic regulation of NFkappaB, and the possible role of NFkappaB activation in ischemia-reperfusion injury, in adaptation to ischemia-reperfusion injury, and in chronic heart failure.