Matrix metalloproteinase-7 affects connexin-43 levels, electrical conduction, and survival after myocardial infarction

Merry L. Lindsey, G. Patricia Escobar, Rupak Mukherjee, Danielle K. Goshorn, Nina J. Sheats, James A. Bruce, I. Matthew Mains, Jennifer K. Hendrick, Kenneth W. Hewett, Robert G. Gourdie, Lynn M. Matrisian, Francis G. Spinale

Research output: Contribution to journalArticlepeer-review

137 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)2919-2928
Number of pages10
Issue number25
StatePublished - Jun 2006
Externally publishedYes


  • Infarction
  • Leukocytes
  • Metalloproteinases
  • Myocardial infarction
  • Remodeling

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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