Cardiac mast cell- and chymase-mediated matrix metalloproteinase activity and left ventricular remodeling in mitral regurgitation in the dog.
The present study tested the hypothesis that cardiac mast cells and chymase are associated with matrix metalloproteinase (MMP) activation and extracellular matrix (ECM) degradation in the evolution of left ventricular (LV) chamber remodeling secondary to experimental mitral regurgitation (MR) in dogs. LV mast cell density, chymase activity, and angiotensin II (ANG II) levels were significantly increased 2 and 4 weeks post-MR, while an increase in angiotensin-converting enzyme (ACE) activity was not seen prior to the chronic 24 week stage. As early as 2 and 4 weeks, there was a significant decrease in interstitial myocardial collagen content that was associated with an increase in LV end-diastolic diameter (LVEDD) but a normal LVEDD/wall thickness ratio. While mast cell density decreased to normal at 24 weeks, both chymase and MMP-2 activity remained increased throughout the entire 24-week period post-MR. By 24 weeks a transition to an adverse pattern of LV remodeling characterized by a 2-fold increase in the LVEDD/wall thickness ratio had occurred. Thus, this study supports the hypothesis that mast cells and chymase are important modulators of MMP activity and ECM degradation, contributing to adverse LV remodeling in chronic volume overload secondary to MR.
Stewart
James A
JA
Department of Anatomy, Physiology, and Pharmacology, 106 Greene Hall, Auburn University, Auburn, AL 36849-5517, USA.
Wei
Chih Chang
CC
Brower
Gregory L
GL
Rynders
Patricia E
PE
Hankes
Gerald H
GH
Dillon
A Ray
AR
Lucchesi
Pamela A
PA
Janicki
Joseph S
JS
Dell'Italia
Louis J
LJ
D000818:Animals; D002452:Cell Count; D053818:Chymases; D004285:Dogs; D004452:Echocardiography; D005260:Female; D006321:Heart / Q000503:physiopathology; D006439:Hemodynamics; D008297:Male; D008407:Mast Cells / Q000201:enzymology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008944:Mitral Valve Insufficiency / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000166:cytology*; D012084:Renin-Angiotensin System; D012697:Serine Endopeptidases / Q000378:metabolism*; D020257:Ventricular Remodeling
D012697:Serine Endopeptidases; D053818:Chymases; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2