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Articles in PresS, published online ahead of print January 24, 2002
Am J Physiol Heart Circ Physiol, 10.1152/ajpheart.00777.2001
Submitted on August 29, 2001
Accepted on January 17, 2002
1 Anatomy, Physiology, and Pharmacology, Auburn University, Auburn, AL, USA
Mast cells contain proteases capable of activating matrix metalloproteinases (MMPs). However, given the relatively low density of mast cells in the myocardium (i.e. 1.5 to 5.3 cells/mm2), it is unknown whether these enzymes are present in sufficient quantities in the normal heart to mediate MMP activation. Accordingly, this study sought to determine if chemically-induced degranulation of cardiac mast cells (with compound 48/80) would have an effect in isolated, blood-perfused, functioning rat hearts. Mast cell degranulation produced a 15% increase in histamine levels present in the coronary efflux, a significant increase in myocardial water (i.e. edema) relative to normal values (80.1 ±3.4 vs. 77.4 ±1.08 %, p 
0.03), a substantial activation of MMP-2 (126 % increase relative to controls, p 0.02), and a marked decrease in myocardial collagen volume fraction (0.46 ±0.10 vs. 0.97 ±0.33%, p 0.001). Furthermore, although an increase in ventricular stiffness was expected due to the extent of edema resulting from mast cell degranulation, modest ventricular dilatation was observed. These findings clearly demonstrate that the number of mast cells present in normal hearts are sufficient to mediate activation of MMPs and produce extracellular matrix degradation, thereby potentially causing subsequent ventricular dilatation.
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