Abstract 1684: Transgenic Matrix Metalloproteinase-2 Expression Increases Myocardial Reperfusion Injury and Abrogates Cardioprotection induced by Ischemic Preconditioning
Background: Matrix metalloproteinase-2 (MMP-2) is postulated to play a central role in the progression of dysfunctional ventricular remodeling. However, the effect of MMP-2 transgenic (Tg) expression in acute ischemia-reperfusion (I/R) injury has not been investigated.
Hypothesis: MMP-2 disturbs cell salvage mechanisms and intensifies tissue injury during myocardial reperfusion.
Methods and Results: MMP-2 Tg mice at the age of 6 months showed no gross alteration of cardiac phenotype compared to age-matched wild-type littermates (WT) examined by histopathology and both ex vivo and in vivo assessments. However, buffer perfused MMP-2 Tg hearts subjected to 30 min of global ischemia followed by 30 min of reperfusion demonstrated significantly greater evidence of myocardial injury. In addition, cardioprotection-mediated by ischemic preconditioning (IPC) was completely abolished in MMP-2 Tg hearts, as shown by abnormalities in mitochondrial ultrastructure and impaired respiration, increased infarct size, creatine kinase (CK) release, lipid peroxidation, and depressed recovery of contractile performance during post-ischemic reperfusion.
Chronic Tg expression of MMP-2 exacerbated acute I/R injury and abolished IPC-mediated cardioprotection.
Impaired mitochondrial function and excessive lipid peroxidation may be important contributors to this outcome.