期刊
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
卷 282, 期 6, 页码 H2152-H2158出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.00777.2001
关键词
compound 48/80; isolated heart; coronary flow; histamine; collagen volume fraction; pressure-volume relationship; matrix metalloproteinase
资金
- NHLBI NIH HHS [R01-HL-62228] Funding Source: Medline
Mast cells contain proteases capable of activating matrix metalloproteinases (MMPs). However, given the relatively low density of mast cells in the myocardium (i.e., 1.5-5.3 cells/mm(2)), 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 whether 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 less than or equal to 0.03), a substantial activation of MMP-2 (126% increase relative to controls, P less than or equal to 0.02), and a marked decrease in myocardial collagen volume fraction (0.46 +/- 0.10% vs. 0.97 +/- 0.33%, P less than or equal to 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 is sufficient to mediate activation of MMPs and produce extracellular matrix degradation, thereby potentially causing subsequent ventricular dilatation.
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