Single‐cell transcriptomic analyses of skin vascular endothelial cells in sedentary and voluntary wheel running young mice

Physical activity (PA) is a fundamental aspect of preventive medicine, offering profound benefits for cardiovascular health and overall well-being. Despite its widespread benefits, the molecular mechanisms underlying PA-induced improvements in microvascular functions remain poorly understood. The skin microvasculature is uniquely affected by exercise-induced shear stress, especially during thermoregulation. We assigned 20 mice to either a sedentary group or a 1-month voluntary exercise program involving running wheels. We assessed endothelial function in mesenteric arteries and found no significant difference between groups, consistent with prior reports of minimal vascular effects from short-term PA in young healthy mice. Post-intervention, we collected skin biopsies from 12 mice for single-cell transcriptomic analyses. The differential expression analysis showed a significant difference in the expression of the Zbtb16 gene in vascular endothelial cells (vECs), with higher levels in the physically active group. Additionally, Gene Set Enrichment Analysis (GSEA) with nominally differentially expressed genes in vECs highlighted the suppression of pathways related to oxidative stress, cell proliferation, and metabolism in the exercise group. This suggests an exercise-triggered transition towards improved metabolic efficiency and enhanced homeostasis in vECs. These results begin to reveal transcriptomic differences in vECs of the skin microvasculature between physically active and sedentary mice.