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Echocardiographic and Histological Examination of Cardiac Morphology in the Mouse
Published on: October 26, 2017
Interstitial remodeling in beta1-adrenergic receptor transgenic mice
Ute Seeland1, Simina Selejan, Stefan Engelhardt
1Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätsklinikum des Saarlandes Klinik für Innere Medizin III, 66421, Homburg/Saar, Germany. seeland@med-in.uni-sb.de
Basic Research in Cardiology
|November 24, 2006
Summary
Sympathetic overactivation triggers matrix remodeling and fibrosis in the heart by increasing matrix metalloproteinase (MMP) activity. Specifically, MMP-2 activity is linked to ventricular dilatation and heart failure development.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Fibrosis Research
Background:
- Inhibiting matrix metalloproteinase (MMP) activity may prevent ventricular dilatation by reducing collagen turnover and fibrosis.
- This study examines MMP/TIMP activity during the transition from cardiac hypertrophy to ventricular dilatation.
Purpose of the Study:
- Investigate the time-course of MMP/TIMP activity in transgenic mice overexpressing the beta1-adrenergic receptor (beta1TG).
- Correlate MMP activity with cardiac hypertrophy, fibrosis, and ventricular dilatation progression.
Main Methods:
- Utilized picro Sirius red staining and real-time PCR for collagen quantification.
- Assessed MMP activity (zymography) and expression (immunoblotting, real-time PCR) for various MMPs and TIMPs.
- Measured integrin-linked kinase (ILK) expression to assess beta1-integrin activity.
Main Results:
- beta1TG mice showed a significant increase in collagen type I and III expression, leading to moderate and severe fibrosis.
- Increased expression of collagenases (MMP-1, -13) and gelatinase (proMMP-2) was observed during hypertrophy.
- Maximal MMP-2 activity and MT1-MMP coexpression correlated with severe fibrosis and ventricular dilatation at 12 months.
Conclusions:
- Sympathetic overactivation induces interstitial matrix remodeling and fibrosis via MMP/TIMP activity.
- Gelatinolytic MMP-2 activity is a key factor accompanying ventricular dilatation and heart failure progression.
