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(Circulation. 1999;100:1462-1463.)
© 1999 American Heart Association, Inc.

Correspondence

Activation of Nuclear Factor-B in Unstable Angina

Nicholas Jenkins, MB ChB, MRCP

Wythenshawe Hospital Manchester, UK

	Introduction

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To the Editor:

The recent study by Ritchie¹ provides evidence of systemic nuclear factor-B (NF-B) activation in patients with unstable angina undergoing coronary arteriography and is in agreement with other clinical studies demonstrating systemic immunologic activation. The major difficulty in interpreting these findings is one of distinguishing cause from effect; rather than reflecting a predisposition to subsequent plaque disruption, NF-B activation may be the consequence of other subsequent processes, including platelet activation or myocardial ischemia. Increased platelet-leukocyte adhesion can be demonstrated in patients with acute coronary syndromes, and in vitro studies demonstrate NF-B activation in leukocytes exposed to thrombin-stimulated platelets.² NF-B activation may also occur indirectly as a consequence of myocardial ischemia or necrosis and in response to myocardial synthesis of pro-inflammatory cytokines during ischemia-reperfusion.³ Prospective studies are needed to prevent these confounding influences and allow an assessment of the true clinical significance of NF-B activation in patients with coronary artery disease.

	References

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1. Ritchie ME. Nuclear factor-B is selectively and markedly activated in humans with unstable angina pectoris. Circulation. 1998;98:1707–1713.[Abstract/Free Full Text]
   
2. Neumann F-J, Marx N, Gawaz M, Brand K, Ott I, Rokitta C, Sticherling C, Meinl C, May A, Schomig A. Induction of cytokine expression in leukocytes by binding of thrombin-stimulated platelets. Circulation. 1997;95:2387–2394.[Abstract/Free Full Text]
   
3. Meldrum DR, Cleveland JC Jr, Cain BS, Meng X, Harken AH. Increased myocardial tumor necrosis factor- in a crystalloid-perfused model of cardiac ischemia-reperfusion injury. Ann Thorac Surg. 1998;65:439–443.[Abstract/Free Full Text]
   

Response

Michael E. Ritchie, MD

Associate Professor of Medicine Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, Ind

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I thank Dr Jenkins for his response to my article.¹ I agree that it is difficult to distinguish cause from effect with regard to NF-B activation in humans with unstable angina pectoris, particularly considering the data cited both in Dr Jenkins' letter and my article showing that events subsequent to plaque rupture can activate NF-B. However, on the basis of the serendipitous observation noted in the article that 2 patients with clinically stable coronary artery disease who subsequently became clinically unstable with serial angiograms showing acute plaque rupture had marked activation of NF-B, I am optimistic that NF-B activation precedes the acute event. Retrospective 5-year follow-up analyses showing a direct relationship between NF-B levels of activation and events (death, myocardial infarction, and unstable angina), regardless of initial clinical presentation, further support this conjecture (J. Gillespie, unpublished data, 1999). Admittedly, neither article directly addresses the "cause or effect" position of NF-B. Accordingly, the site of NF-B activation in the coronary bed in stable and unstable patients, its capacity to predict subsequent coronary artery events, and its effectiveness as a target for therapy are being prospectively analyzed. These experiments should begin to clarify the role of NF-B in the progression of atherosclerosis, its role in plaque rupture, and most importantly, its clinical applicability.

	References

Top Introduction References Introduction  References

 

1. Ritchie ME. Nuclear factor-B is selectively and markedly activated in humans with unstable angina pectoris. Circulation. 1998;98:1707–1713.
   

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