Voluntary running induces fiber type-specific angiogenesis in mouse skeletal muscle

Abstract

Adult skeletal muscle undergoes adaptation in response to endurance exercise, including fast-to-slow fiber type transformation and enhanced angiogenesis. The purpose of this study was to determine the temporal and spatial changes in fiber type composition and capillary density in a mouse model of endurance training. Long-term voluntary running (4 wk) in C57BL/6 mice resulted in an approximately twofold increase in capillary density and capillary-to-fiber ratio in plantaris muscle as measured by indirect immunofluorescence with an antibody against the endothelial cell marker CD31 (466 +/- 16 capillaries/mm2 and 0.95 +/- 0.04 capillaries/fiber in sedentary control mice vs. 909 +/- 55 capillaries/mm2 and 1.70 +/- 0.04 capillaries/fiber in trained mice, respectively; P < 0.001). A significant increase in capillary-to-fiber ratio was present at day 7 with increased concentration of vascular endothelial growth factor (VEGF) in the muscle, before a significant increase in percentage of type IIa myofibers, suggesting that exercise-induced angiogenesis occurs first, followed by fiber type transformation. Further analysis with simultaneous staining of endothelial cells and isoforms of myosin heavy chains (MHCs) showed that the increase in capillary contact manifested transiently in type IIb + IId/x fibers at the time (day 7) of significant increase in total capillary density. These findings suggest that endurance training induces angiogenesis in a subpopulation of type IIb + IId/x fibers before switching to type IIa fibers.

Testing Metabolic Theories

“…The metabolic rate of small species following endurance training should therefore be relatively Body mass (kg) Post-training relative capillary density Figure 6: Relationship between post-endurance-training capillary density, expressed relative to capillary density of untrained individuals, and body mass. Data are from published studies, including a range of training durations, methods, and intensities (Hermansen and Wachtlova 1971;Andersen and Henriksson 1977;Ingjer 1979;Adolfsson et al 1981;Klausen et al 1981;Hoppeler et al 1984Hoppeler et al , 1985Essén-Gustavsson et al 1989;Bigard et al 1991;Rivero et al 1995;McCall et al 1996;Serrano et al 2000;Amaral et al 2001;Waters et al 2004;Chinsomboon et al 2009;Geng et al 2010). …”

Cardiac Vasculature: Development and Pathology

“…Angiogenesis in the setting of the adult heart can be regulated by hypoxia-induced responses through HIF-1a, that can directly regulate endothelial cell activity and increase capillary density (Pugh CW and Ratcliffe PJ, 2003). Another mechanism is associated with a general stress response following acute hemodynamic overload or hypertrophy induced by exercise or pregnancy (HilfikerKleiner D et al, 2005;Jacobs TB et al, 1984;Sano M et al, 2007;Waters RE et al, 2004). This response would allow the myocardium to coordinate an increase in microvessels with an ensuing hypertrophic response.…”

The Effect of Caffeine Supplementation on Exercise Performance Evaluated by a Novel Animal Model

“…Experiments for assessment of each single animal performance are more complex, demanding equipment for swimming, treadmills, and other devices [11][12][13][14][15][16] . The utility of grouped voluntary exercise is more evident in the evaluation of interventions that increase or decrease the propensity to exercise.…”

“…For rodents, this is a potent stressor 10,11 . Other types of models force the animals to run in treadmills [12][13][14] , using electric shocks 15,16 or brushes 17 to motivate them. An extensive literature search did not find experiments utilizing grouped animals and adding their combined activity to assess exercise performance or propensity that could be used to compare in animals, point by point, the seven conclusions derived by the International Society of Sports Nutrition from humans 18 .…”