Myocardial infarction in sheep induced region-specific changes in matrix metalloproteinases, including a >300% increase in MMP-13, MMP-8, and MT1-MMP in the transition and MI regions (P<0.05).
p-value: p=<0.05
BACKGROUND: Induction of matrix metalloproteinases (MMPs) contributes to adverse remodeling after myocardial infarction (MI). Whether a region- and type-specific distribution of MMPs occurs within the post-MI myocardium remained unknown. METHODS AND RESULTS: Ten sheep were instrumented with a sonomicrometry array to measure dimensions in 7 distinct regions corresponding to the remote, transition, and MI regions. Eight sheep served as reference controls. The relative abundance of representative MMP types and the tissue inhibitors of the MMPs (TIMPs) was quantified by immunoblotting. Segment length increased from baseline in the remote (24.9+/-5.4%), transition (18.0+/-2.9%), and MI (53.8+/-11.0%) regions at 8 weeks after MI (P300% in the transition and MI regions (P<0.05). TIMP abundance decreased significantly in the transition region after MI and fell to undetectable levels within the MI region. CONCLUSIONS: The unique findings of this study were 2-fold. First, changes in regional geometry after MI were associated with changes in MMP levels. Second, a region-specific portfolio of MMPs was induced after MI and was accompanied by a decline in TIMP levels, indicative of a loss of MMP inhibitory control. Targeting the regional imbalance between specific MMPs and TIMPs within the post-MI myocardium holds therapeutic potential.
Wilson et al. (Wed,) conducted a other in Myocardial infarction (n=18). Myocardial infarction vs. Reference controls was evaluated on Segment length changes and relative abundance of MMPs and TIMPs (p=<0.05). Myocardial infarction in sheep induced region-specific changes in matrix metalloproteinases, including a >300% increase in MMP-13, MMP-8, and MT1-MMP in the transition and MI regions (P<0.05).