43Matrix metalloproteinase-9 deletion shifts macrophage polarization towards M2 phenotype in aged left ventricles post-myocardial infarction

Matrix metalloproteinase (MMP)-9 increases in the aging left ventricle (LV) post-myocardial infarction (MI). Post-MI, macrophages produce MMP-9 and regulate the inflammatory response and extracellular matrix deposition. We hypothesized that increasing age would prime macrophage polarization towards the M1 pro-inflammatory phenotype post-MI, which may be attenuated by MMP-9 deletion. We enrolled WT and MMP-9 Null (Null) young (4-5 month old) and old (15-24 month old) mice (n=6/age/genotype). We performed permanent occlusion of the left coronary descending artery to induce MI. Mice were sacrificed at day 7 post-MI, and macrophages were isolated from the infarcted area. RT2-PCR was used to quantify pro-inflammatory M1 (Ccl3 and IL1-β) and anti-inflammatory M2 (CD163) markers. Old MI mice of both genotypes showed higher Ccl3 levels than young mice (both p<0.05). Post-MI, old WT mice showed a significant increase in IL1-β levels, which was attenuated by MMP-9 deletion (all p<0.05; Figure 1, A). This suggests that aging induced M1 macrophage polarization in the post-MI LV, and this effect was modulated by MMP-9. Additionally, MMP-9 deletion resulted in the increase of CD163 in old mice post-MI compared to young null and age-matched WT control groups (all p<0.05; Figure 1, B), suggesting enhanced M2 polarization in the old Nulls. In conclusion, our findings indicate that aging promotes inflammation post-MI, and this effect is attenuated by MMP-9 deletion. Identifying how MMP-9 regulates LV remodeling post-MI may provide new potential therapeutic options for the aging MI patient. Open in new tabDownload slide