Abstract 15381: Matrix Metalloproteinase-28 Deletion Exacerbates Cardiac Dysfunction and Rupture Following Myocardial Infarction in Mice
Matrix metalloproteinase (MMP)-28 regulates the inflammatory and extracellular matrix (ECM) responses in cardiac aging. The objective of this study is to explore the role of MMP-28 in myocardial infarction (MI). Adult C57BL/6J wild type (WT, n=64) and MMP-28-/- (n=72) mice of both sexes were subjected to permanent coronary artery ligation. MMP-28 expression decreased post-MI, and its cell source shifted from myocyte to macrophage. The 7 d survival rate was 58% (14/24) for WT and 29% (10/34) for MMP-28-/- mice (p<0.05). Autopsy evaluation revealed that 40% of non-surviving WT mice died of rupture of the left ventricle (LV), while the rupture rate was 88% in MMP-28-/- mice (p<0.05), most of which are male. Compared to WT d 7 post-MI, MMP-28-/- mice had larger LV volumes (p<0.05) and lower ejection fraction (p<0.05). The MMP-28-/- mice also showed worse LV remodeling and lung edema. Plasma MMP-9 levels in WT significantly increased at d 7, compared to d 0 (p<0.05), but this increase in MMP-9 did not occur in the MMP-28-/- mice. Inflammatory and ECM gene array analysis revealed that MMP-28-/- mice at d 7 had lower inflammatory factors and ECM transcription than WT. MMP-28 deletion led to decreased collagen deposition and myofibroblast numbers. The expression and activation of lysyl oxidase at d 7 post-MI were inhibited in MMP-28-/- mice. Male MMP-28-/- hearts at d 3 post-MI showed no difference in tensile strength, compared with WT. In conclusion, MMP-28 deletion aggravated post-MI LV dysfunction and rupture due to impaired inflammatory response and scar formation.
- © 2012 by American Heart Association, Inc.