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J Am Coll Cardiol, 1998; 32:606-612
© 1998 by the American College of Cardiology Foundation
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CLINICAL STUDIES

Mast cell infiltration in acute coronary syndromes: implications for plaque rupture

Maija Kaartinen, MD* {dagger}, Allard C. van der Wal, MD{ddagger}, Chris M. van der Loos, PhD{ddagger}, Jan J. Piek, MD§, Karel T. Koch, MD§, Anton E. Becker, MD, FACC{ddagger} and Petri T. Kovanen, MD*

* Wihuri Research Institute, Helsinki, Finland
{dagger} Division of Cardiology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland
{ddagger} Department of Cardiovascular Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
§ Department of Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands

Manuscript received October 15, 1997; revised manuscript received April 30, 1998, accepted May 13, 1998.

Address for correspondence: Dr. Petri T. Kovanen, Wihuri Research Institute, Kalliolinnantie 4, 00140 Helsinki, Finland

Objectives. To define the role of mast cells in plaque destabilization.

Background. Inflammation is an essential feature of human coronary plaques. Macrophages and T lymphocytes are considered to contribute to destabilization of the plaques. The role of mast cells in this setting is less well studied. We therefore counted the mast cells in coronary atherectomy specimens from patients with chronic stable angina, unstable angina and severe unstable angina.

Methods. Patients studied had chronic stable angina (group 1, n = 11), "stabilized" unstable angina (group 2; Braunwald’s class I and II, n = 11) and "refractory" unstable angina (group 3; Braunwald’s class III, n = 7). Samples of culprit lesions (n = 29) were obtained by directional atherectomy, snap-frozen and analyzed immunohistochemically. The numbers of mast cells and T lymphocytes per square millimeter squared were counted and the areas containing macrophages and smooth muscle cells were measured by computed planimetry.

Results. We found that the numbers of mast cells and T lymphocytes increased from group 1 through groups 2 to 3. Specimens from group 3 also contained the largest numbers of tumor necrosis factor alpha (TNF-{alpha})-positive mast cells and of matrix metalloproteinase (MMP)-9 (92 kD gelatinase)-positive macrophages.

Conclusions. Unstable coronary syndromes are associated with increased numbers of mast cells in culprit lesions. Activated mast cells secrete neutral proteases capable of degrading the extracellular matrix and TNF-{alpha}, capable of stimulating macrophages to synthesize MMP-9. Our observations suggest that mast cells, in addition to macrophages, contribute to matrix degradation and, hence, to progression of coronary syndromes.

Abbreviations and Acronyms
  DCA = directional coronary atherectomy
  MMP = matrix metalloproteinase
  TNF-{alpha} = tumor necrosis factor alpha




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