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

About the project:

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 cells (mEC) populations which 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 to 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.

Read the article at

Information available on the Explorer:

TSNE and Violin plots: Visualization of gene expression and cell type information of mECs in TSNE and Violin plots. Atlas clustering is based on an unbiased mapping to soleus sample of   Kalucka et al.

3D TSNE: 3D visualization of gene expression and cell type information of mECs for a better interpretation of the structure of the data.

Mouse bulk RNAseq: Visualization of normalized gene counts of ECs from oxidative (RmECs) and glycolytic (WmECs) muscle in WT and ATF4 KO cells. Full RNAseq data of each comparison is available to download.

Contact information:

For questions or suggestions about the project, please contact Prof. Dr. Katrien De Bock at   katrien-debock@ethz.ch

Website developed and maintained by Guillermo Turiel. For website questions, suggestions or issues, please contact Guillermo Turiel at   guillermo.turiel@hest.ethz.ch