| First Author | Fan Z | Year | 2021 |
| Journal | Cell Metab | Volume | 33 |
| Issue | 9 | Pages | 1793-1807.e9 |
| PubMed ID | 34358431 | Mgi Jnum | J:309733 |
| Mgi Id | MGI:6759719 | Doi | 10.1016/j.cmet.2021.07.015 |
| Citation | Fan Z, et al. (2021) Exercise-induced angiogenesis is dependent on metabolically primed ATF3/4(+) endothelial cells. Cell Metab 33(9):1793-1807.e9 |
| abstractText | 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 ATF3/4(low) 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 ATF3/4(low) 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. |
