Senescence regulates macrophage activation and angiogenic fate at sites of tissue injury in mice
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Abnormal angiogenesis plays a key role in diseases of aging such as heart disease, certain cancers, and eye diseases including age-related macular degeneration. Macrophages have been shown previously to be both anti- and proangiogenic, and their role in regulating angiogenesis at sites of tissue injury is critical and complex. In this study, we analyzed cytokine gene expression patterns of mouse macrophages by real-time quantitative PCR and tested the functional effects of senescence on gene expression and macrophage polarization. Following laser injury to the retina, IL-10 was upregulated and Fas ligand (FasL), IL-12, and TNF-alpha were downregulated in ocular macrophages of old mice (>18 months of age). Downregulation of FasL on macrophages led to a loss of the antiangiogenic phenotype, as evidenced by the inability of these macrophages to inhibit vascular endothelial cells. Our results demonstrate that senescence, FasL, and IL-10 are key determinants of macrophage function that alter the growth of abnormal postdevelopmental blood vessels in disease processes including blinding eye disease.
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Macrophages from old mice are more proangiogenic than macrophages from young mice.
“Indeed, macrophages from old mice are more proangiogenic as compared to young macrophages (59).”
From The impact of ageing on monocytes and macrophages (2021) · cites this paper as [59]
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Khan, A. A., Dace, D. S., Ryazanov, A. G., Kelly, J., & Apte, R. S. (2010) · American Journal Of Pathology · doi:10.2353/ajpath.2010.090836 · Cited by 57 · see citing works
Inflammation in the pathogenesis of age-related macular degeneration
Kanda, A., Abecasis, G. R., & Swaroop, A. (2008) · British Journal of Ophthalmology · doi:10.1136/bjo.2007.131581 · Cited by 55 · see citing works
Complement regulation in the eye: implications for age-related macular degeneration
Wilke, G. A., & Apte, R. S. (2024) · Journal of Clinical Investigation · doi:10.1172/jci178296 · Cited by 54 · see citing works
Aredo, B., Zhang, K., Chen, X., Wang, C. X.-Z., Li, T., & Ufret-Vincenty, R. L. (2015) · Journal of Neuroinflammation · doi:10.1186/s12974-014-0221-4 · Cited by 53 · see citing works
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Cellular senescence in the tumor microenvironment and context‐specific cancer treatment strategies
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Innate immunity and cellular senescence: The good and the bad in the developmental and aged brain
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- Authors
- Kelly, J., Khan, A. A., Yin, J., Ferguson, T. A., & Apte, R. S.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Apte, Rajendra S.
- Venue
- Journal of Clinical Investigation
- Published
- 2007-11-01
- Volume
- 117
- Issue
- 11
- Pages
- 3421-3426
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC2045608
- OpenAlex
- W2000811703
- Cited by
- 249
- References
- 15
- Citations by year
- 2026: 12 · 2025: 11 · 2024: 12 · 2023: 14 · 2022: 20 · 2021: 12 · 2020: 9 · 2019: 15 · 2018: 24 · 2017: 14 · 2016: 9 · 2015: 13 · 2014: 13 · 2013: 16 · 2012: 11
- FWCI
- 4.37
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
- Funders
- Research to Prevent Blindness (EY02687)
- National Institutes of Health (5p60dk020579-35, DK20579, P60-DK-20579, EY02687, 5 P60 DK20579, EY06765)
- National Eye Institute (EY 02687, P30EY002687, EY 12826, K08EY016139, R01EY012826, F32EY006765, EY06765, R01EY006765)
- National Institute of Diabetes and Digestive and Kidney Diseases (5P60 DK20579, P60-DK-020579)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Keywords
- cellular senescence, macrophage activation, angiogenesis, tissue damage, Fas ligand, IL-10, macrophage polarization, cytokine gene expression, age-related macular degeneration, vascular endothelial cells, aging
- MeSH terms
- Aging, Animals, Gene Expression Regulation, Humans, Lasers, Macrophage Activation, Macrophages, Mice, Inbred C57BL, Retina, Cytokines, Interleukin-10, Cellular Senescence, Mice, Knockout, Choroidal Neovascularization, Mice
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