期刊
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
卷 45, 期 1, 页码 56-61出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.yjmcc.2008.04.010
关键词
mast cells; collagen; matrix metalloproteinases; cytokines; rodent
资金
- NCI NIH HHS [R37 CA071382-10, R37 CA071382, CA-71382] Funding Source: Medline
- NHLBI NIH HHS [R01-HL-62228, R01 HL062228, HL-73990, R01 HL073990] Funding Source: Medline
Mast cells have diverse roles throughout the body as evidenced by their heterogeneous nature. In the heart, cardiac mast cells have been implicated in left ventricular (LV) remodeling in response to elevated myocardial stress. Accordingly, the purpose of this study was to use mast cell deficient rats (Ws/Ws) to delineate the interaction between cardiac mast cell activation and LV remodeling. LV matrix metalloproteinase (MMP) activity, fibrillar collagen, TNF-alpha levels, and LV diameter were compared in Ws/Ws and wild type (WT) rats subjected to 5 d (n = 3/group) and 8 weeks (n = 4/group) of aortocaval fistula-induced volume overload. In contrast to attenuation of myocardial remodeling in the Ws/Ws group: 1) MMP-2 activity was significantly increased in the WT group at 5 days; 2) there was marked degradation of the extracellular collagen matrix in WT at 5 days and 8 weeks; 3) the percent increase in LV diameter from baseline was significantly greater in WT at 2, 4, 6, and 8 weeks post-fistula; and 4) myocardial TNF-alpha levels were markedly elevated in the WT group at 5 days post-fistula. These results underscore the importance of cardiac mast cells in mediating MMP activation, collagen degradation and LV dilatation and suggest that mast cell-derived TNF-alpha plays a role in early myocardial remodeling. (C) 2008 Elsevier Inc. All rights reserved.
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