In Endurance Training, VEGF Production Precedes Angiogenesis, and Angiogenesis Precedes Changes of Fiber Type

Experiments using laboratory mice complement those of human subjects in studies of the effects of endurance training. Researchers followed the time course of changes in the plantaris muscle over a period of 28 days. (The plantaris lies beneath the gastrocnemius muscle of the lower leg.) They found that VEGF production occurred within 3 days of the start of running and was followed by increased numbers of capillaries after about 7 days. The conversion of the fastest muscle fibers to intermediate Type IIa fibers was complete after 14 days. Data from these experiments appear in Box Extension 21.1.

Male mice (8 weeks old) were housed individually in cages with running wheels. The wheels of control (sedentary) mice were locked so they would not rotate. The wheels of endurance-trained mice were connected to a data-acquisition system that measured the distance run by each mouse. The mice ran voluntarily and clocked an average of 10 km/day. Mice ran for 1, 3, 7, 14, or 28 days. Five or six mice were included in test and control groups. At the end of each test period, the plantaris muscle was removed and used to analyze muscle fiber types, capillary density, and concentration of VEGF. The data illustrate the expected increase in capillary density and conversion from the fastest fiber types (Type IIb and also a mouse fiber type called IId/x) to the fast oxidative Type IIa (see the figure). Whereas the sedentary animals’ plantaris muscles had about 83% of the fastest fiber types, the plantaris muscles of animals trained for 28 days showed a reduction of the fastest fiber types to about 67%. The reduction of the fastest fibers was accompanied by an increase in the fast oxidative Type IIa from about 15% to about 32%. The plantaris muscle is classified as a fast-twitch muscle and includes only about 2% of slow Type I fibers. The proportion of Type I fibers did not change during training. No cell death occurred, and the researchers concluded that the fastest fibers transformed into Type IIa fibers. The data provide an intriguing record of the time course of changes that occurred over a month of endurance training. The sequence of changes was first a rise in VEGF (day 3), then a significant rise in capillary density (day 7), and finally an increase in Type IIa fibers (day 14). These data correlate the presence of VEGF and the occurrence of angiogenesis, and they suggest that angiogenesis precedes the conversion of fiber types. The researchers raise the interesting question of whether or not increased density of capillaries around a particular muscle fiber may permit or promote its switch to a slower type.

Changes in VEGF, angiogenesis, and muscle fiber type in endurance-trained mice Data are means ± S.E.M., and * indicates a significant difference from the control (0 days of training): P < 0.05 (VEGF), P < 0.01 (capillaries), P < 0.001 (fiber abundance). (After Waters et al. 2004.)