血管生成
ATF3
细胞生物学
体内
骨骼肌
糖酵解
癌症研究
化学
生物
新陈代谢
内分泌学
生物化学
基因表达
遗传学
基因
发起人
作者
Zheng Fan,Guillermo Turiel,Raphaela Ardicoglu,Moheb Ghobrial,Evi Masschelein,Tea Kocijan,Jing Zhang,Ge Tan,G. Kelley Fitzgerald,Tatiane Gorski,Abdiel Alvarado-Diaz,Paola Gilardoni,Christopher M. Adams,Bart Ghesquière,Katrien De Bock
出处
期刊:Cell Metabolism
[Elsevier]
日期:2021-09-01
卷期号:33 (9): 1793-1807.e9
被引量:30
标识
DOI:10.1016/j.cmet.2021.07.015
摘要
Exercise is a powerful driver of physiological angiogenesis during adulthood, but the mechanisms of exercise-induced vascular expansion are poorly understood. We explored endothelial heterogeneity in skeletal muscle and identified two capillary muscle endothelial cell (mEC) populations that are characterized by differential expression of ATF3/4. Spatial mapping showed that ATF3/4+ mECs are enriched in red oxidative muscle areas while ATF3/4low ECs lie adjacent to white glycolytic fibers. In vitro and in vivo experiments revealed that red ATF3/4+ mECs are more angiogenic when compared with white ATF3/4low mECs. Mechanistically, ATF3/4 in mECs control genes involved in amino acid uptake and metabolism and metabolically prime red (ATF3/4+) mECs for angiogenesis. As a consequence, supplementation of non-essential amino acids and overexpression of ATF4 increased proliferation of white mECs. Finally, deleting Atf4 in ECs impaired exercise-induced angiogenesis. Our findings illustrate that spatial metabolic angiodiversity determines the angiogenic potential of muscle ECs.
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