REVIEW ARTICLE
Nuclear factor kappa-B and the heart
Guro Valen, MD, PhD*,
Zhong-qun Yan, PhD and
G.öran K. Hansson, MD, PhD
* Crafoord Laboratory of Experimental Surgery, Karolinska Hospital, Stockholm, Sweden
Center of Molecular Medicine, Karolinska Hospital, Stockholm, Sweden
Manuscript received November 29, 2000;
revised manuscript received April 11, 2001,
accepted April 25, 2001.
Reprint requests and correspondence: Dr. Guro Valen, Crafoord Laboratory of Experimental Surgery L6:00, Karolinska Hospital, S-171 76 Stockholm, Sweden Guro.Valen{at}cmm.ki.se
Nuclear factor kappa-B (NF B), a redox-sensitive transcription factor regulating a battery of inflammatory genes, has been indicated to play a role in the development of numerous pathological states. Activation of NF B induces gene programs leading to transcription of factors that promote inflammation, such as leukocyte adhesion molecules, cytokines, and chemokines, although some few substances with possible anti-inflammatory effects are also NF B regulated. The present article reviews basic regulation of NF B and its activation, cell biological effects of NF B activation and the role of NF B in apoptosis. Evidence involving NF B as a key factor in the pathophysiology of ischemia-reperfusion injury and heart failure is discussed. Although activation of NF B induces pro-inflammatory genes, it has lately been indicated that the transcription factor is involved in the signaling of endogenous myocardial protection evoked by ischemic preconditioning. A possible role of NF B in the development of atherosclerosis and unstable coronary syndromes is discussed. Nuclear factor kappa-B may be a new therapeutic target for myocardial protection.
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Abbreviations and Acronyms
| | IAP | = inhibitor of apoptosis | | ICAM | = intercellular adhesion molecule | | IL | = interleukin | I B | = inhibitory kappa-B | | IKK | = inhibitory kappa-B kinase complex | | LPS | = lipopolysaccharide | | MAPK | = mitogen-activated protein kinase | NF B | = nuclear factor kappa-B | | NO | = nitric oxide | | TLR | = toll-like receptor | TNF- | = tumor necrosis factor-alpha | | XIAP | = X-linked inhibitor of apoptosis protein |
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