Protection from adverse myocardial remodeling secondary to chronic volume overload in mast cell deficient rats. J Mol Cell Cardiol 2008 Jul;45(1):56-61
Date
06/10/2008Pubmed ID
18538342Pubmed Central ID
PMC3272272DOI
10.1016/j.yjmcc.2008.04.010Scopus ID
2-s2.0-45549090007 (requires institutional sign-in at Scopus site) 59 CitationsAbstract
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.
Author List
Levick SP, Gardner JD, Holland M, Hauer-Jensen M, Janicki JS, Brower GLMESH terms used to index this publication - Major topics in bold
AnimalsArteriovenous Shunt, Surgical
Dilatation
Enzyme Activation
Fibrillar Collagens
Heart Diseases
Male
Mast Cells
Matrix Metalloproteinase 2
Myocardium
Rats
Rats, Mutant Strains
Tumor Necrosis Factor-alpha
Ventricular Remodeling
