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From the Division of Cardiology and Cardiovascular Research Center,
University of Cincinnati College of Medicine, and Division of Cardiology,
Veterans Administration Medical Center, Cincinnati, Ohio.
Correspondence to Michael E. Ritchie, MD, University of Cincinnati College of Medicine, 231 Bethesda Ave, ML 0542, Cincinnati, OH 45267-0532. E-mail Michael.Ritchie{at}uc.edu
Background—Nuclear factor-
Methods and Results—Evidence of NF-
Conclusions—These data show that NF-
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Nuclear Factor-
B Is Selectively and Markedly Activated in Humans With Unstable Angina Pectoris
B
(NF-B) resides inactive in the cytoplasm of lymphocytes, monocytes,
endothelial cells, and smooth muscle cells, where,
after stimulation, it transcriptionally activates interleukins,
interferon, tumor necrosis factor-
, and adhesion molecules. Because
acute inflammation may play a role in coronary artery plaque
rupture, it was hypothesized that NF-B activation correlated with
coronary artery disease (CAD) activity. B activation in the
circulation of 102 consecutive patients without an acute myocardial
infarction who were undergoing cardiac catheterization
was determined. Of these, 19 had unstable angina (USA) and were within
24 hours of the last episode of chest pain. The remaining 83 were being
evaluated for stable angina (53), valvular heart disease (8),
atypical chest pain (12), or congestive heart failure (10).
Evidence of NF-B activation was determined by electromobility
shift assays (EMSAs) with the NF-B binding-site–specific probe and
nuclear proteins isolated from the buffy coat of blood obtained at the
beginning of the procedure. Specificity of this DNA-protein interaction
was confirmed by competition and supershift EMSAs. Analyses
showed that 17 of 19 patients with USA had marked activation of
NF-B. Despite a significant number of patients with severe CAD
(69%), only 2 of the 83 without USA showed marked NF-B activation.
A lack of NF-B activation was not due to a lack of functional
cell/protein because NF-B was appropriately activated by
lipopolysaccharide ex vivo in all patients. NF-B activation
was not a nonspecific response of all transcription factors because
neither Sp1 or Oct1 was activated in patients with
activated NF-B. There was no relationship between drugs
used, hemodynamic status, or other clinical
characteristics and state of NF-B activation. B is specifically and
significantly activated in unstable angina pectoris and is not
affected by severity of CAD or medical therapy. Furthermore, because
NF-B is activated before a clinical event, it may be
mechanistically involved in the plaque disruption that produces acute
coronary artery syndromes.
Key Words: angina • inflammation • NF-kappa B • coronary disease
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