Abstract 14526: Matrix Metalloproteinase-28 Deletion Preserves Cardiac Function Following Myocardial Infarction in Mice
Matrix Metalloproteinase-28 (MMP-28, epilysin) is the newest member of MMP family and is constitutively expressed in multiple normal adult tissues, suggesting a role in tissue homeostasis. Previous evidence has revealed that in response to skin injury, MMP-28 expression is up-regulated at both proximal and distal sites from the wound edge to regulate wound repair. However, the role of MMP-28 in remodeling of the left ventricle following myocardial infarction (MI) has not been demonstrated. We hypothesized that MMP-28 deficiency would improve cardiac dysfunction triggered by MI. In this study, we compared wild type (WT) and MMP-28-/- mice at day 0, day 1, and day 5 post-MI. MMP-28 protein was mainly expressed by myocytes at day 0, but by macrophages at day 5 post-MI. Both WT and MMP-28-/- mice had similar infarct sizes at day 1 (55±2% vs 53±2%, n= 9/group) and at day 5 (49±2% vs 50±2%, n= 7/group) post-MI. Cardiac function assessed by echocardiography was significantly deteriorated following MI in both genotypes. However, ejection fraction was markedly improved in MMP-28-/- mice compared to WT mice at day 1 (23±1% for MMP-28-/- vs 17±2% for WT, p<0.05) and at day 5 (17±1% for MMP-28-/- vs 12±1% for WT, p<0.05) post-MI. Plasma proteomic profiling demonstrated that circulating MMP-9 levels were significantly increased from 80±7 ng/ml at day 0 to 133±15 ng/ml at day 1 after MI in WT mice (p<0.05), but this increase did not occur in the MMP-28-/- mice. Plasma TIMP-1 levels were markedly elevated at day 1 and 5 post-MI in both genotypes (p<0.05), compared to day 0 controls. However, TIMP-1 levels were significantly lower in MMP-28-/- mice at day 5 post-MI (3.2±0.3 ng/ml), compared to WT mice (4.8±0.8 ng/ml, p<0.05). In conclusion, MMP-28 deletion improves MI-induced cardiac dysfunction, in part by regulating macrophage function and attenuating MMP-9 levels.
- © 2011 by American Heart Association, Inc.