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- Title
Myocardial Infarction Superimposed on Aging: MMP-9 Deletion Promotes M2 Macrophage Polarization.
- Authors
Yabluchanskiy, Andriy; Yonggang Ma; DeLeon-Pennell, Kristine Y.; Altara, Raffaele; Halade, Ganesh V.; Voorhees, Andrew P.; Nguyen, Nguyen T.; Yu-Fang Jin; Winniford, Michael D.; Hall, Michael E.; Hai-Chao Han; Lindsey, Merry L.; Ma, Yonggang; Jin, Yu-Fang; Han, Hai-Chao
- Abstract
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.
- Subjects
AGE factors in myocardial infarction; PHYSICAL activity -- Social aspects; METALLOPROTEINASES; HEALTH of older people; GENE expression; LABORATORY mice; AGING; ANIMAL experimentation; CYTOKINES; ECHOCARDIOGRAPHY; IMMUNOHISTOCHEMISTRY; LIGATURE (Surgery); MICE; MYOCARDIAL infarction; POLYMERASE chain reaction; PROTEOLYTIC enzymes; SURVIVAL analysis (Biometry); VENTRICULAR remodeling
- Publication
Journals of Gerontology Series A: Biological Sciences & Medical Sciences, 2016, Vol 71, Issue 4, p475
- ISSN
1079-5006
- Publication type
journal article
- DOI
10.1093/gerona/glv034