Abstract 15285: Matrix Metalloproteinase-9 Deletion Blunts Inflammation and Facilitates Scar Formation Post-Myocardial Infarction in the Aging Left Ventricle
Matrix metalloproteinase (MMP)-9 increases in the aging left ventricle (LV) post-MI, and MMP-9 deletion attenuates LV remodeling and improves cardiac function in young mice post-MI. We hypothesized that MMP-9 deletion would attenuate inflammation and LV remodeling in aging mice post-MI. We enrolled 192 C57BL/6J (wt) and 195 MMP-9 null (null) mice of both sexes. The age spread was 11 to 36 months, which in humans compares to 30 to 100 years of age. MI was induced in 91 wt and 95 null mice, and the mice were analyzed at 7 days post-MI. We used 101 wt and 100 null mice for day 0 aging only comparisons. At baseline, the wt mice showed evidence of cardiac sarcopenia, which was improved in the null mice. The infarct area was similar between wt and null groups (47±7% for wt and 46±6% for null; p=0.338). Survival rate for wt males was 45% and for wt females was 62% (p<0.05). Null mice showed improved survival, which was 85% for both males and females (p<0.05). The extent of LV dilation was attenuated in null mice, as evidenced by a 13±1% lower end-systolic dimension (p<0.05) and 8±1% lower end-diastolic dimension (p<0.05) compared to wt day 7 post-MI. Null mice showed increased plasma levels of DCP-2, MIP-1 alpha, IL1-alpha (all p<0.05), which in late stages post-MI contribute to angiogenesis and scar formation. Null mice lowered the LV levels of ccr1, pf4, ccl9, cx3cl1, il8rb, ccl17, ccl11, and Il1r2 gene expression (all p<0.05), which indicated reduced inflammation in the nulls post-MI. Null mice showed higher levels of cadherin 2, collagen 1 alpha 1, and collagen 3 alpha 1 gene expression at day 7 post-MI compared to day 0 and day 7 post-MI wt mice (all p<0.05), indicating that scar formation was enhanced in the null group. Our findings demonstrate that MMP-9 deletion attenuated age-associated inflammation and facilitated post-MI scar formation in aging mice to improve cardiac performance.
- © 2013 by American Heart Association, Inc.