Glycolysis links reciprocal activation of myeloid cells and endothelial cells in the retinal angiogenic niche

著者: Zhiping Liu, Jiean Xu, Qian Ma, Xiaoyu Zhang, Qiuhua Yang, Lina Wang, Yapeng Cao, Zhimin Xu, Amany Tawfik, Ye Sun, Neal L. Weintraub, David Fulton, Mei Hong, Zheng Dong, Lois E. H. Smith, Ruth B. Caldwell, Akrit Sodhi, Yuqing Huo - Science Translational Medicine 2020 被引用: 182

for rodents), a glycolytic activator in myeloid cells, impaired the ability of macrophages/microglia to acquire an angiogenic phenotype, rendering them unable to promote EC proliferation and sprouting and pathological neovascularization in a mouse model of oxygen-induced proliferative retinopathy. Mechanistically, hyperglycolytic macrophages/microglia produced large amount of acetyl-coenzyme A, leading to histone acetylation and PRAGM-related gene induction, thus reprogramming macrophages/microglia into an angiogenic phenotype. These findings reveal a critical role of glycolytic metabolites as initiators of reciprocal activation of macrophages/microglia and ECs in the retinal angiogenic niche and suggest that strategies targeting the metabolic communication between these cell types may be efficacious in the treatment of pathological retinal angiogenesis.