Cited by 249Angiogenesis and VEGF in CancerRetinal Diseases and TreatmentsTelomeres, Telomerase, and Senescence

Senescence regulates macrophage activation and angiogenic fate at sites of tissue injury in mice

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Kelly, Jennifer, Khan, Aslam Ali, Yin, Jiyi, Ferguson, Thomas A., Apte, Rajendra S.·2007·Journal of Clinical Investigation

Abstract

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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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)
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
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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