期刊
AGING-US
卷 6, 期 5, 页码 399-413出版社
IMPACT JOURNALS LLC
DOI: 10.18632/aging.100669
关键词
Cardiac macrophages; inflammation; cardiac senescence; Cx3cr1; tissue macrophages; ageing
资金
- Stem Cells Australia
- Australian Research Council
- National Heart Foundation of Australia [G 12M 6627]
- State Government of Victoria
- Australian Government
Cardiac tissue macrophages (cTMs) are abundant in the murine heart but the extent to which the cTM phenotype changes with age is unknown. This study characterizes aging-dependent phenotypic changes in cTM subsets. Using the Cx3cr1(GFP/+) mouse reporter line where GFP marks cTMs, and the tissue macrophage marker Mrc1, we show that two major cardiac tissue macrophage subsets, Mrc1(-)GFPhi and Mrc1(+)GFP(hi) cTMs, are present in the young (<10 week old) mouse heart, and a third subset, Mrc1(+)GFP(lo), comprises similar to 50% of total Mrc1(+) cTMs from 30 weeks of age. Immunostaining and functional assays show that Mrc1(+) cTMs are the principal myeloid sentinels in the mouse heart and that they retain proliferative capacity throughout life. Gene expression profiles of the two Mrc1(+) subsets also reveal that Mrc1(+) GFPlo cTMs have a decreased number of immune response genes (Cx(3)cr1, Lpar6, CD9, Cxcr4, Itga6 and Tgf beta r1), and an increased number of fibrogenic genes (Ltc4s, Retnla, Fgfr1, Mmp9 and Ccl24), consistent with a potential role for cTMs in cardiac fibrosis. These findings identify early age-dependent gene expression changes in cTMs, with significant implications for cardiac tissue injury responses and aging-associated cardiac fibrosis.
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