Myocardial infarction superimposed on aging: MMP-9 deletion promotes M2 macrophage polarization

Andriy Yabluchanskiy, Yonggang Ma, Kristine Y. Deleon-Pennell, Raffaele Altara, Ganesh V. Halade, Andrew P. Voorhees, Nguyen T. Nguyen, Yu Fang Jin, Michael D. Winniford, Michael E. Hall, Hai Chao Han, Merry L. Lindsey

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)475-483
Number of pages9
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume71
Issue number4
DOIs
StatePublished - Apr 1 2016

Keywords

  • Aging
  • Cardiac remodeling
  • M2 phenotype
  • Macrophage polarization

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology

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