Exercise-induced angiogenesis is dependent on metabolically primed ATF3/4+ endothelial cells

• DOI: 10.1016/j.cmet.2021.07.015
• Publication Date: 2021-08-05T14:32:56Z
• Authors: 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
• Keywords: ATF3

Exercise is a powerful driver of physiological angiogenesis during adulthood, but the mechanisms exercise-induced vascular expansion are poorly understood. We explored endothelial heterogeneity in skeletal muscle and identified two capillary cell (mEC) populations that characterized by differential expression ATF3/4. Spatial mapping showed ATF3/4+ mECs enriched red oxidative areas while ATF3/4low ECs lie adjacent to white glycolytic fibers. In vitro vivo experiments revealed more angiogenic when compared with mECs. Mechanistically, ATF3/4 control genes involved amino acid uptake metabolism metabolically prime (ATF3/4+) for angiogenesis. As consequence, supplementation non-essential acids overexpression ATF4 increased proliferation Finally, deleting Atf4 impaired Our findings illustrate spatial metabolic angiodiversity determines potential ECs.