INDUCTION AND MAINTENANCE OF INCREASED VEGF PROTEIN BY CHRONIC MOTOR-NERVE STIMULATION IN SKELETAL-MUSCLE

Vascular endothelial growth factor (VEGF) causes endothelial cell prol iferation in vitro and angiogenesis in vivo. Glycolytic skeletal muscl es have a lower capillary density than oxidative muscles but can incre ase their capillary density and convert to a more oxidative phenotype when subject to chronic motor nerve stimulation (CMNS). We used Wester n analysis and immunohistochemical techniques to examine VEGF protein in a rabbit CMNS model of glycolytic skeletal muscle and in muscles wi th innate glycolytic ver sus oxidative phenotypes. VEGF protein per gr am of total protein was increased in stimulated vs. control muscles 2. 9 +/- 1.0, 3.6 +/- 1.3, 3.1 +/- 0.5, 4.4 +/- 1.6, and 2.7 +/- 0.3 time s after 3 (n = 4), 5 (n = 2), 10 (n = 3), 21 (n = 3), and 56 (n = 2) d ays, respectively. VEGF protein was increased 3.1 +/- 0.5 times (P < 0 .005) before (3, 5, and 10 days) and remained elevated 3.7 +/- 1.0 tim es (P < 0.05) after (21 and 56 days) the transition to an oxidative ph enotype. By immunohistochemistry, VEGF protein was found primarily in the matrix between stimulated muscle fibers but not in the myocytes. I n addition, VEGF protein was consistently lower in innate glycolytic c ompared with oxidative muscles. These findings suggest that VEGF plays a role in the alteration and maintenance of vascular density in mamma lian skeletal muscles.