Disruption of the myocardial extracellular matrix leads to cardiac dysfunction
Henry E. Kim, … , Myron L. Weisfeldt, Jeanine D’Armiento
Henry E. Kim, … , Myron L. Weisfeldt, Jeanine D’Armiento
Published October 1, 2000
Citation Information: J Clin Invest. 2000;106(7):857-866. https://doi.org/10.1172/JCI8040.
View: Text | PDF
Article

Disruption of the myocardial extracellular matrix leads to cardiac dysfunction

Abstract

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.

Authors

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

×

Figure 6

Options: View larger image (or click on image) Download as PowerPoint
Upregulation of collagen type III but not collagen type I in cardiac-col...
Upregulation of collagen type III but not collagen type I in cardiac-collagenase mice. Northern blot analysis was performed using 10 μg total RNA from heart tissue from transgenic (line WH 1) and wild-type littermate mice at 6-week, 6-month, and 12-month time points and probed with an xba I/Hind III fragment of the collagen type III cDNA (top). Increased collagen III message was detected in the transgenic mice compared with the wild-type littermates at the 6-week time point. No difference was noted by the 6- month or 12-month time point. The same membrane was probed with a Hind III fragment of the collagen type I cDNA (middle). No differences in type I collagen expression were observed between wild-type and transgenic mice at any time point. The lower panel shows the same membranes probed with ribosomal 28S oligonucleotide to ensure that equal amounts of RNA were loaded in each lane. WT, wild-type, TG, transgenic.