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J Am Coll Cardiol, 2001; 38:307-314
© 2001 by the American College of Cardiology Foundation
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REVIEW ARTICLE

Nuclear factor kappa-B and the heart

Guro Valen, MD, PhD*, Zhong-qun Yan, PhD{dagger} and G.öran K. Hansson, MD, PhD{dagger}

* Crafoord Laboratory of Experimental Surgery, Karolinska Hospital, Stockholm, Sweden
{dagger} 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{kappa}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{kappa}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{kappa}B regulated. The present article reviews basic regulation of NF{kappa}B and its activation, cell biological effects of NF{kappa}B activation and the role of NF{kappa}B in apoptosis. Evidence involving NF{kappa}B as a key factor in the pathophysiology of ischemia-reperfusion injury and heart failure is discussed. Although activation of NF{kappa}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{kappa}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.

Abbreviations and Acronyms
  IAP = inhibitor of apoptosis
  ICAM = intercellular adhesion molecule
  IL = interleukin
  I{kappa}B = inhibitory kappa-B
  IKK = inhibitory kappa-B kinase complex
  LPS = lipopolysaccharide
  MAPK = mitogen-activated protein kinase
  NF{kappa}B = nuclear factor kappa-B
  NO = nitric oxide
  TLR = toll-like receptor
  TNF-{alpha} = tumor necrosis factor-alpha
  XIAP = X-linked inhibitor of apoptosis protein




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