Antiangiogenic effect of interleukin-10 in ischemia-induced angiogenesis in mice hindlimb
Abstract
Ischemia induces both hypoxia and inflammation that trigger angiogenesis. The inflammatory reaction is modulated by production of anti-inflammatory cytokines. This study examined the potential role of a major anti-inflammatory cytokine, interleukin (IL)-10, on angiogenesis in a model of surgically induced hindlimb ischemia. Ischemia was produced by artery femoral occlusion in both C57BL/6J IL-10(+/+) and IL-10(-/-) mice. After 28 days, angiogenesis was quantified by microangiography, capillary, and arteriole density measurement and laser Doppler perfusion imaging. The protein levels of IL-10 and vascular endothelial growth factor (VEGF) were determined by Western blot analysis in hindlimbs. IL-10 was markedly expressed in the ischemic hindlimb of IL-10(+/+) mice. Angiogenesis in the ischemic hindlimb was significantly increased in IL-10(-/-) compared with IL-10(+/+) mice. Indeed, angiographic data showed that vessel density in the ischemic leg was 10.2+/-0.1% and 5.7+/-0.4% in IL-10(-/-) and IL-10(+/+) mice, respectively (P:<0.01). This corresponded to improved ischemic/nonischemic leg perfusion ratio by 1.4-fold in IL-10(-/-) mice compared with IL-10(+/+) mice (0.87+/-0. 05 versus 0.63+/-0.01, respectively; P:<0.01). Revascularization was associated with a 1.8-fold increase in tissue VEGF protein level in IL-10(-/-) mice compared with IL-10(+/+) mice (P:<0.01). In vivo electrotransfer of murine IL-10 cDNA in IL-10(-/-) mice significantly inhibited both the angiogenic process and the rise in VEGF protein level observed in IL-10(-/-) mice. No changes in vessel density or VEGF content were observed in the nonischemic hindlimb. These findings underscore the antiangiogenic effect of IL-10 associated with the downregulation of VEGF expression and suggest a role for the inflammatory balance in the modulation of ischemia-induced angiogenesis.
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- Authors
- Silvestre, J.-S., Mallat, Z., Duriez, M., Tamarat, R., Bureau, M. F., Scherman, D., Duverger, N., Branellec, D., Tedgui, A., & Levy, B. I.
- Affiliations
- From INSERM U541, Hôpital Lariboisière, Institut Fédératif de Recherche “Circulation, Paris 7” (J.S.S., Z.M., M.D., R.T., A.T., B.I.L.), Paris; Unité Mixte de Recherche 7001, Centre National de la Recherche Scientifique/ENSCP/Aventis, Aventis Gencell (M.F.B., D.S.), Vitry; and Aventis Gencell (N.D., D.B.), Vitry, France.
- Centre National de la Recherche Scientifique (FR)
- Venue
- Circulation Research
- Published
- 2000-09-15
- Volume
- 87
- Issue
- 6
- Pages
- 448-452
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- OpenAlex
- W2167186712
- Cited by
- 210
- References
- 22
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 3 · 2023: 5 · 2022: 7 · 2021: 5 · 2020: 7 · 2019: 3 · 2018: 8 · 2017: 7 · 2016: 11 · 2015: 16 · 2014: 12 · 2013: 7 · 2012: 6
- FWCI
- 3.85
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Institut National de la Santé et de la Recherche Médicale
- Université Paris Diderot
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Health Sciences › Medicine › Surgery › Peripheral Artery Disease Management
- Keywords
- IL-10, angiogenesis, hindlimb ischemia, vascular endothelial growth factor, anti-inflammatory cytokines, inflammation, revascularization, IL-10 knockout mice, electrotransfer, femoral artery occlusion, tissue perfusion, capillary density, hypoxia
- MeSH terms
- Animals, Arterioles, Capillaries, Hindlimb, Ischemia, Lymphokines, Male, Mice, Inbred C57BL, Endothelial Growth Factors, Interleukin-10, Laser-Doppler Flowmetry, Gene Transfer Techniques, DNA, Complementary, Muscle, Skeletal, Neovascularization, Physiologic, Vascular Endothelial Growth Factors, Vascular Endothelial Growth Factor A, Mice
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