Abstract 15925: The Unique Membrane Type-1 Matrix Metalloproteinase is Constitutively Active Within the Human Myocardial Interstitium and Dynamically Changes with Ischemia-Reperfusion
Background: A unique member of the matrix metalloproteinases (MMPs) includes the membrane-type-1 MMP (MT1-MMP), and basic studies have identified a cause-effect relation between MT1-MMP induction and changes in LV remodeling/function following ischemia-reperfusion (I/R). However, since MT1-MMP is membrane bound, then direct assessment of MT1-MMP activity (MT1-MMPact) within the human myocardial interstitial space has not been performed. Using a novel fluorogenic-microdialysis approach, the present study tested the hypothesis that MT1-MMPact is constitutively active within the human myocardial interstitium and dynamically changes with I/R.
Methods/Results: The present study directly quantified interstitial MT1-MMPact within the myocardium of patients (n=10) undergoing elective cardiac surgery during steady-state conditions, as well as during and following an obligatory period of I/R achieved by cardiopulmonary bypass (CPB). Interstitial MT1-MMP activity was continuously measured as the fluorescence emission from a specific and validated MT1-MMP fluorogenic substrate, a microdialysis probe placed within the myocardium, and an in-line detection system. MT1-MMPact could be readily detected within the human myocardial interstitium, and a representative real-time recording is shown (Figure) which demonstrated a small oscillatory pattern to MT1-MMPact. Following the induction of myocardial arrest with reperfusion (post-CPB) a significant increase in MT1-MMPact occurred and this change is summarized for all patients (Figure, inset).
Conclusions: This study for the first time demonstrated that MT1-MMP activity is constitutively active within the human myocardial interstitium and changes in a rapid and dynamic fashion under conditions such as transient ischemia-reperfusion. In light of the diverse biological functions of MT1-MMP, these findings hold relevance in the context of regulation of myocardial structure and function.
- © 2010 by American Heart Association, Inc.