Myocardial Infarction Superimposed on Aging: Mmp-9 Deletion Promotes M2 Macrophage Polarization
Aging, Cardiac remodeling, M2 phenotype, Macrophage polarization
Digital Object Identifier (DOI)
In this study, we examined the combined effect of aging and myocardial infarction on left ventricular remodeling, focusing on matrix metalloproteinase (MMP)-9-dependent mechanisms. We enrolled 55 C57BL/6J wild type (WT) and 85 MMP-9 Null (Null) mice of both sexes at 11-36 months of age and evaluated their response at Day 7 post-myocardial infarction. Plasma MMP-9 levels positively linked to age in WT mice (r = .46, p = .001). MMP-9 deletion improved survival (76% for WT vs 88% for Null, p = .021). Post-myocardial infarction, there was a progressive increase in left ventricular dilation with age in WT but not in Null mice. By inflammatory gene array analysis, WT mice showed linear age-dependent increases in three different proinflammatory genes (C3, CCl4, and CX3CL1; all p < .05), whereas Null mice showed increases in three proinflammatory genes (CCL5, CCL9, and CXCL4; all p < .05) and seven anti-inflammatory genes (CCL1, CCL6, CCR1, IL11, IL1r2, IL8rb, and Mif; all p < .05). Compared with WT, macrophages isolated from Null left ventricle infarct demonstrated enhanced expression of anti-inflammatory M2 markers CD163, MRC1, TGF-β1, and YM1 (all p < .05), without affecting proinflammatory M1 markers. In conclusion, MMP-9 deletion stimulated anti-inflammatory polarization of macrophages to attenuate left ventricle dysfunction in the aging post-myocardial infarction.
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Citation / Publisher Attribution
Journals of Gerontology - Series A Biological Sciences and Medical Sciences, v. 71, issue 4, p. 475-483
Scholar Commons Citation
Yabluchanskiy, Andriy; Ma, Yonggang; Deleon-Pennell, Kristine Y.; Altara, Raffaele; Halade, Ganesh V.; Voorhees, Andrew P.; Nguyen, Nguyen T.; Jin, Yu Fang; Winniford, Michael D.; Hall, Michael E.; Han, Hai Chao; and Lindsey, Merry L., "Myocardial Infarction Superimposed on Aging: Mmp-9 Deletion Promotes M2 Macrophage Polarization" (2016). Internal Medicine Faculty Publications. 39.