瑞士联邦理工学院Katrien De Bock团队的最新研究发现运动诱导的血管生成依赖于代谢诱导的ATF3/4+内皮细胞。2021年8月5日，国际学术期刊《细胞-代谢》在线发表了这一成果。
研究人员探索了骨骼肌的内皮异质性，并确定了两种毛细血管内皮细胞 (mEC) 群，其特征在于ATF3/4的差异表达。空间映射显示ATF3/4+ mECs富含红色氧化肌肉区域，而 ATF3/4low ECs位于白色糖酵解纤维附近。体外和体内实验表明，与白色ATF3/4low mEC相比，红色ATF3/4+ mEC具有更强的血管生成能力。
从机制上讲，mECs中的ATF3/4控制参与氨基酸摄取和代谢相关的基因，并通过代谢诱发与血管生成相关的红色 (ATF3/4+) mECs。因此，补充非必需氨基酸和过表达ATF4都可以增加白色mEC的增殖。最后，敲除ECs中的Atf4基因会损害运动诱导的血管生成。这项研究结果表明，空间代谢血管多样性决定了肌肉ECs的血管生成潜力。
据介绍，运动是成年个体生理血管生成的强大驱动力，但对运动诱导血管扩张的机制知之甚少。
附：英文原文
Title: Exercise-induced angiogenesis is dependent on metabolically primed ATF3/4+ endothelial cells
Author: Zheng Fan, Guillermo Turiel, Raphaela Ardicoglu, Moheb Ghobrial, Evi Masschelein, Tea Kocijan, Jing Zhang, Ge Tan, Gillian Fitzgerald, Tatiane Gorski, Abdiel Alvarado-Diaz, Paola Gilardoni, Christopher M. Adams, Bart Ghesquière, Katrien De Bock
Issue&Volume: 2021-08-05
Abstract: 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.
DOI: 10.1016/j.cmet.2021.07.015
Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(21)00331-4
Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
官方网址：https://www.cell.com/cell-metabolism/home
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本期文章：《细胞—代谢》：Online/在线发表
