Genetics shift the angio‐adaptive balance in skeletal muscle of mice selected for high running capacity

Abstract

Selective breeding for voluntary wheel running has resulted in mice with high inherited exercise capacity, which have been termed “mini muscle’ (MM) mice based on a small myofiber phenotype. We tested the hypothesis that an altered angiogenic expression profile would explain increased capillarity in MM compared to control (WT) mice. A subset of each group (N=5–8) were also acutely exercised for 1‐hr to test the angiogenic responsiveness to exercise. Gastrocnemius (GA) and plantaris (PLT) muscle capillarity were greater in MM vs WT (P<0.05). MM mice had 58% and 79% greater basal vascular endothelial growth factor (VEGF) protein in GA and PLT, respectively (P<0.05). Basal thrombospondin‐1 (TSP‐1) was unchanged in the GA, but 39% lower in PLT (P<0.05) of MM vs WT. In response to acute exercise, MM mice showed a 41% and 28% increase in VEGF in the GA and PLT, respectively (P<0.05). TSP‐1 protein was decreased by 90% in GA (P<0.05), but increased 50% in PLT (P<0.05). In contrast, there was no VEGF or TSP‐1 response to acute exercise in the GA of WT mice; however TSP‐1, but not VEGF, increased by 47% in the PLT of WT mice. An altered balance in basal VEGF and TSP‐1 correlates with greater capillarity in these selectively bred mice. These data suggest that basal expression and the response of key angiogenic regulators may be genetically influenced and account for the greater capillarity/enhanced exercise capacity in MM mice.