Disruption of the myocardial extracellular matrix leads to cardiac dysfunction

Henry E. Kim, Seema S. Dalal, Erik Young, Marianne J. Legato, Myron L. Weisfeldt, Jeanine D'Armiento

Research output: Contribution to journalArticlepeer-review

221 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)857-866
Number of pages10
JournalJournal of Clinical Investigation
Issue number7
StatePublished - Oct 2000
Externally publishedYes

ASJC Scopus subject areas

  • General Medicine


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