Skeletal muscle fiber‐type, enzyme activity, and angiogenesis are altered in exercise trained mice deficient in muscle VEGF

Abstract

Vascular endothelial growth factor (VEGF) is required for maintaining capillary number in adult mouse skeletal muscle. Muscle capillarity and endurance exercise capacity is reduced in cre/loxP mediated muscle VEGF knock-out (myoVEGF−/−) mice. To test the importance of myocyte VEGF in exercise training, we accessed muscle adaptations to exercise training in myoVEGF−/− and wild-type (WT) mice following a 6-week training regime. Training consisted of 1-hr treadmill run, 5-d/wk, where myoVEGF−/− and WT mice ran at the same absolute speed/incline and work intensity gradually increased from 10 m/min, 0° incline (wk 1) to 22 m/min, 10° incline (wk 6). In WT mice, testing of maximal running speed increased following training (33.5 ± 1.2 to 36.3 ± 1.4 m/min, p<0.05, mean±SEM), but only small, non-significant, rises in capillary-to-fiber ratio, C:F (1.24 ± 0.18 to 1.40 ± 0.25, p=n.s.) and capillary density, CD (36 ± 5 to 56 ±9 #/mm2, p=0.10) were seen in the gastrocnemius muscle. Fiber type composition remained unaltered. In myoVEGF−/−, training did not alter maximal running speed tests (23.0 ± 1.2 to 24.6 ± 1.1 m/min), C:F (0.65 ± 0.10 to 0.61 ± 0.07), or CD (22 ± 2 to 29 ± 3 #/mm2); however, % of type IIA fibers tended to decrease (81 ± 4% to 72 ± 3%, p=0.07) while % of type IIB fibers increased (12 ± 4% to 23 ± 3%, p<0.05). Type I fibers (6 ±1% to 5 ± 1%) were unchanged. Phosphofructokinase (PFK) enzyme activity was greater in myoVEGF−/− than WT (86.7±5.1 vs. 72.3±3.7 mmol/kg/min, p<0.05) muscle. These data suggest that myoVEGF−/− mice have a greater reliance on glycolytic metabolism during exercise; and that in the absence of muscle VEGF, the potential for skeletal muscle angioadaptation to physical training is lost. Funding AHA 0365103Y, NIH 17731, Parker B. Francis Foundation.