期刊
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
卷 35, 期 12, 页码 2638-2646出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/ATVBAHA.115.306543
关键词
cytokines; endothelial cell; inflammation; interleukins; oxygen-induced retinopathy
资金
- Ministry of Science and Technology of China [2015CB964600, 2013CB967500]
- National Natural Science Foundation of China [31470038, 31300741]
- Fundamental Research Funds for the Central Universities
- Research Fund for the Doctoral Program of Higher Education of China [20130072120030]
- Foundation for the Young Talents by Tongji University [2013KJ054]
Objective Angiogenesis is tightly controlled by growth factors and cytokines in pathophysiological settings. Interleukin 37 (IL-37) is a newly identified cytokine of the IL-1 family, some members of which are important in inflammation and angiogenesis. However, the function of IL-37 in angiogenesis remains unknown. We aimed to explore the regulatory role of IL-37 in pathological and physiological angiogenesis. Approach and Results We found that IL-37 was expressed and secreted in endothelial cells and upregulated under hypoxic conditions. IL-37 enhanced endothelial cell proliferation, capillary formation, migration, and vessel sprouting from aortic rings with potency comparable with that of vascular endothelial growth factor. IL-37 activates survival signals including extracellular signal-regulated kinase 1/2 and AKT in endothelial cells. IL-37 promoted vessel growth in implanted Matrigel plug in vivo in a dose-dependent manner with potency comparable with that of basic fibroblast growth factor. In the mouse model of retinal vascular development, neonatal mice administrated with IL-37 displayed increased neovascularization. We demonstrated further that IL-37 promoted pathological angiogenesis in the mouse model of oxygen-induced retinopathy. Conclusions Our findings suggest that IL-37 is a novel and potent proangiogenic cytokine with essential role in pathophy siological settings.
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