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Cardiac mast cell-mediated activation of gelatinase and alteration of ventricular diastolic function

Amanda L Chancey1, Gregory L Brower, Joseph S Janicki

  • 1Department of Anatomy, Physiology, and Pharmacology, Auburn University, Auburn, Alabama 36849, USA.

American Journal of Physiology. Heart and Circulatory Physiology
|May 11, 2002
PubMed

Insights

Cardiac mast cells, though sparse, can activate matrix metalloproteinases (MMPs). Degranulation induced myocardial edema, MMP-2 activation, and extracellular matrix degradation, potentially leading to ventricular dilatation.

Area of Science:

  • Cardiovascular Biology
  • Cellular Biology
  • Biochemistry

Background:

  • Mast cells reside in the myocardium and contain proteases that can activate matrix metalloproteinases (MMPs).
  • The functional significance of cardiac mast cells in activating MMPs within the normal heart remains unclear due to their relatively low density.

Purpose of the Study:

  • To investigate the effect of chemically induced cardiac mast cell degranulation on MMP activation and extracellular matrix in an isolated rat heart model.
  • To determine if the quantity of mast cells in a normal heart is sufficient to mediate MMP activation and extracellular matrix degradation.

Main Methods:

  • Isolated, blood-perfused, functioning rat hearts were utilized.
  • Cardiac mast cell degranulation was chemically induced using compound 48/80.
  • Histamine levels, myocardial water content, MMP-2 activation, and collagen volume fraction were measured.

Main Results:

  • Mast cell degranulation increased coronary efflux histamine levels by 15%.
  • Myocardial water content significantly increased, indicating edema (80.1% vs 77.4%).
  • MMP-2 activation substantially increased (126%), and myocardial collagen volume fraction markedly decreased (0.46% vs 0.97%).
  • Modest ventricular dilatation was observed despite expected stiffness from edema.

Conclusions:

  • The number of mast cells in normal hearts is sufficient to activate MMPs.
  • Cardiac mast cell degranulation leads to extracellular matrix degradation.
  • This degradation has the potential to cause subsequent ventricular dilatation.

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