Increased capillary tortuosity and pericapillary basement membrane thinning in skeletal muscle of mice undergoing running wheel training

Abstract

To work out which microvascular remodeling processes occur in murine skeletal muscle during endurance exercise, we subjected C57BL/6-mice to voluntary running wheel training for 1 week (1wk-t) or 6 weeks (6wks-t). By means of morphometry, the capillarity as well as the compartmental and sub-compartmental structure of the capillaries were quantitatively described at the light microscopy and at the electron microscopy level, respectively, in the plantaris muscle (PLNT) of the exercising mice in comparison to untrained littermates. In the early phase of the training (1wk-t), angiogenesis (32%-higher capillary-fiber (CF)-ratio; P<0.05) in PLNT was accompanied by a tendency of capillary lumen enlargement (30%; P=0.06) and reduction of the pericapillary basement membrane thickness (CBMT; 12.7%; P=0.09) as well as a 21%-shortening of intraluminal protrusion length (P<0.05), all compared to controls. After long-term training (6wks-t), when the mice reached a steady state in running activity, additional angiogenesis (CF-ratio: 76%; P<0.05) and a 16.3%-increase in capillary tortuosity (P<0.05) were established, accompanied by reversal of the lumen expansion (23%; P>0.05), further reduction of CBMT (16.5%; P<0.05) and additional shortening of the intraluminal protrusion length (23%; P<0.05), all compared to controls. Other structural indicators such as capillary profile sizes, profile area densities, perimeters of the capillary compartments and concentrations of endothelium-pericyte peg-socket junctions were not significantly different between the mouse groups. Besides angiogenesis, increase of capillary tortuosity and reduction of CBMT represent the most striking microvascular remodeling processes in skeletal muscle of mice that undergo running wheel training.