MMP activity with disruption of structural collagen has been implicated in the pathophysiology of dilated cardiomyopathy. To examine the role of this enzyme in cardiac function, a transgenic mouse was created that constitutively expressed human collagenase (MMP-1) in the heart. At 6 months of age, these animals demonstrated compensatory myocyte hypertrophy with an increase in the cardiac collagen concentration due to elevated transcription of type III collagen. Chronic myocardial expression of MMP-1 produced loss of cardiac interstitial collagen coincident with a marked deterioration of systolic and diastolic function at 12 months of age. This is the first animal model demonstrating that direct disruption of the extracellular matrix in the heart reproduces the changes observed in the progression of human heart failure.
Henry E. Kim, Seema S. Dalal, Erik Young, Marianne J. Legato, Myron L. Weisfeldt, Jeanine D’Armiento
Title and authors | Publication | Year |
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Diastolic dysfunction and heart failure with a preserved ejection fraction: Relevance in critical illness and anaesthesia
R Maharaj |
Journal of the Saudi Heart Association | 2012 |
Changes in Plasma Profiles of Matrix Metalloproteinases (MMPs) and Tissue Inhibitors of MMPs in Stress-Induced Cardiomyopathy
EM Essa, MR Zile, RE Stroud, A Rice, RJ Gumina, CV Leier, FG Spinale |
Journal of Cardiac Failure | 2012 |
MT1-MMP-dependent remodeling of cardiac extracellular matrix structure and function following myocardial infarction
GC Koenig, RG Rowe, SM Day, F Sabeh, JJ Atkinson, KR Cooke, SJ Weiss |
The American Journal of Pathology | 2012 |
α -Enolase, a Multifunctional Protein: Its Role on Pathophysiological Situations
À Díaz-Ramos, A Roig-Borrellas, A García-Melero, R López-Alemany |
Journal of Biomedicine and Biotechnology | 2012 |