期刊
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
卷 71, 期 4, 页码 475-483出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/gerona/glv034
关键词
Aging; Cardiac remodeling; Macrophage polarization; M2 phenotype
资金
- American Heart Association [13POST14350034]
- National Institutes of Health, National Heart, Lung, and Blood Institute SC2 [HL101430, HL095852]
- National Institutes of Health, National Center for Complementary and Integrative Health [R00AT006704]
- National Institutes of Health [HHSN 268201000036C (N01-HV-00244), R01HL075360, HL051971, GM104357]
- Biomedical Laboratory Research and Development Service of the Veterans Affairs Office of Research and Development Award [5I01BX000505]
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-beta 1, 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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