Expression of angiogenic regulators and skeletal muscle capillarity in selectively bred high aerobic capacity mice

Abstract

Selective breeding for high voluntary wheel running in untrained mice has resulted in a 'mini muscle' (MM) phenotype, which has increased skeletal muscle capillarity compared with muscles from non-selected control lines. Vascular endothelial growth factor (VEGF) and thrombospondin-1 (TSP-1) are essential mediators of skeletal muscle angiogenesis; thus, we hypothesized that untrained MM mice with elevated muscle capillarity would have higher basal VEGF expression and lower basal TSP-1 expression, and potentially an exaggerated VEGF response to acute exercise. We examined skeletal muscle morphology and skeletal muscle protein expression of VEGF and TSP-1 in male mice from two (untrained) mouse lines selectively bred for high exercise capacity (MM and Non-MM), as well as one non-selected control mouse line (normal aerobic capacity). In the MM mice, gastrocnemius (GA) and plantaris (PLT) muscle capillarity (i.e. capillary-to-fibre ratio and capillary density) were greater compared with control mice (P < 0.05). In Non-MM mice, only muscle capillarity in PLT was greater than in control mice (P < 0.001). The soleus (SOL) showed no statistical differences in muscle capillarity among groups. In the GA, MM mice had 58% greater basal VEGF (P < 0.05), with no statistical difference in basal TSP-1 when compared with control mice. In the PLT, MM mice had a 79% increase in basal VEGF (P < 0.05) and a 39% lower basal TSP-1 (P < 0.05) compared with the control animals. Non-MM mice showed no difference in basal VEGF in either the GA or the PLT compared with control mice. In contrast, basal TSP-1 was elevated in the PLT, but not in the GA, of Non-MM mice compared with control mice. Neither VEGF nor TSP-1 was significantly different in SOL muscle among the three mouse lines. In response to acute exercise, MM mice displayed a 41 and 28% increase (P < 0.05) in VEGF in the GA and PLT, respectively, whereas neither control nor Non-MM mice showed a significant VEGF response to acute exercise. In contrast, TSP-1 levels were decreased by 90% in GA (P < 0.05) but increased by 50% in PLT (P < 0.05) in response to acute exercise in MM mice. The SOL showed no response to exercise for either VEGF or TSP-1 for any of the mouse lines. These data, with the exception of the Non-MM plantaris muscle, suggest that elevated capillarity is associated with altered balance between positive and negative angiogenic regulators (i.e. VEGF versus TSP-1, respectively). Based on the greater capillarity and significant VEGF response to exercise in MM mice, these data suggest that VEGF expression may, at least in part, be genetically determined.

Effects of detraining on the temporal expression of positive and negative angioregulatory proteins in skeletal muscle of mice

“…; Audet et al . ; Olfert & Birot, ). The present finding might argue against this idea and suggest that some other mechanism is attenuating the VEGF response to acute exercise.…”

Brain Activation Patterns at Exhaustion in Rats That Differ in Inherent Exercise Capacity

“…By controling the environmental conditions with which animals are housed, researchers are better able to isolate potential “exercise genes” that may contribute to differences in inherent running capacity. To date, most of the research in exercise genomics in animals has focused on cardiac and skeletal muscle adaptations [1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], while the contribution of central mechanisms remains less understood. Because the initiation and processing of locomotor activity occurs within the central nervous system, we hypothesized that alterations in central pathways could also play a role in variation in inherent running capacity between animals.…”

Shear stress‐induced angiogenesis in mouse muscle is independent of the vasodilator mechanism and quickly reversible

“…However, this possibility requires further research as ‘sedentary’ mice selectively bred to have high aerobic exercise capacity with the concomitant elevation in C:F compared to normal mice do not exhibit lower VEGF, but rather unchanged (or higher) basal VEGF protein (Audet et al . 2011). …”