Protection from adverse myocardial remodeling secondary to chronic volume overload in mast cell deficient rats.
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.
Department of Cell and Developmental Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, South Carolina 29208, USA.
Scott P
SP
Levick
Jason D
JD
Gardner
Merrilee
M
Holland
Martin
M
Hauer-Jensen
Joseph S
JS
Janicki
Gregory L
GL
Brower
D000818:Animals; D001166:Arteriovenous Shunt, Surgical / Q000009:adverse effects; D004106:Dilatation; D004789:Enzyme Activation; D024022:Fibrillar Collagens / Q000378:metabolism*; D006331:Heart Diseases / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008407:Mast Cells / Q000378:metabolism* / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D011922:Rats, Mutant Strains; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D020257:Ventricular Remodeling
D024022:Fibrillar Collagens; D014409:Tumor Necrosis Factor-alpha; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat