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Updated: Jan 10, 2026
Disorders of Erythrocytes
Matrix metalloproteinase-7 affects connexin-43 levels, electrical conduction, and survival after myocardial
Merry L Lindsey1, G Patricia Escobar, Rupak Mukherjee
1Cardiology Division, Department of Medicine, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, Mail Code 7872, San Antonio, TX 78229-3900, USA. lindseym@uthscsa.edu
Background:
Matrix metalloproteinases (MMPs) contribute to left ventricular remodeling after myocardial infarction (MI). Specific causative roles of particular MMPs, however, remain unclear. MMP-7 is abundant in cardiomyocytes and macrophages, but MMP-7 function after MI has not been defined.
Methods And Results:
Wild-type (WT; n=55) and MMP-7-null (MMP-7-/-; n=32) mice underwent permanent coronary artery ligation for 7 days. MI sizes were similar, but survival was greatly improved in MMP-7-/- mice. The survival difference could not be attributed to differences in left ventricular dilation because end-diastolic volumes increased similarly. ECG analysis revealed a prolonged PR interval in WT but not in MMP-7-/- post-MI mice. Post-MI conduction velocity, determined by optically mapping electrical wavefront propagation, decreased to 78+/-6% of control for WT and was normalized in MMP-7-/- mice. In WT mice, slower conduction velocity correlated with a 53% reduction in the gap junction protein connexin-43. Direct binding of MMP-7 to connexin-43, determined by surface plasmon resonance technology, occurred in a dose-dependent manner. Connexin-43 processing by MMP-7 was confirmed by in silico and in vitro substrate analyses and MMP-7 infusion induced arrhythmias in vivo.
Conclusions:
MMP-7 deletion results in improved survival and myocardial conduction patterns after MI. This is the first report to implicate MMP-7 in post-MI remodeling and to demonstrate that connexin-43 is a novel MMP-7 substrate.
Insights
Matrix metalloproteinase-7 (MMP-7) deletion improves survival after myocardial infarction (MI) by normalizing cardiac conduction. This study identifies MMP-7 as a key factor in post-MI remodeling and connexin-43 processing.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Cardiac Remodeling
Background:
- Matrix metalloproteinases (MMPs) are implicated in left ventricular remodeling post-myocardial infarction (MI).
- The specific roles of individual MMPs, particularly MMP-7, in MI pathogenesis remain largely undefined.
- MMP-7 is expressed in cardiomyocytes and macrophages, suggesting potential involvement in cardiac injury.
Purpose of the Study:
- To investigate the functional role of MMP-7 in the cardiac response to myocardial infarction.
- To determine the impact of MMP-7 deficiency on post-MI survival, cardiac remodeling, and electrical conduction.
- To identify potential molecular targets of MMP-7 in the context of MI.
Main Methods:
- Comparison of wild-type and MMP-7-null mice subjected to permanent coronary artery ligation.
- Assessment of survival rates, left ventricular remodeling (end-diastolic volume), and cardiac electrical activity (ECG, optical mapping).
- Analysis of connexin-43 expression and interaction with MMP-7 using surface plasmon resonance, in silico, and in vitro methods.
Main Results:
- MMP-7-null mice exhibited significantly improved survival post-MI compared to wild-type controls.
- Left ventricular dilation and end-diastolic volumes were similar between groups, indicating survival benefits were not due to reduced dilation.
- MMP-7 deficiency normalized post-MI cardiac conduction velocity and prevented PR interval prolongation, correlating with preserved connexin-43 levels.
- Direct binding and processing of connexin-43 by MMP-7 were demonstrated, with MMP-7 infusion inducing arrhythmias in vivo.
Conclusions:
- Deletion of MMP-7 significantly enhances survival and improves myocardial electrical conduction patterns following MI.
- This study establishes MMP-7 as a critical mediator in post-MI cardiac remodeling.
- Connexin-43 is identified as a novel substrate for MMP-7, providing a molecular mechanism for MMP-7's detrimental effects post-MI.
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