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

1 Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham 27710; and 3 Division of Cardiology, Department of Medicine, Durham Department of Veterans Affairs Medical Center, Durham, North Carolina 27705; and 2 Department of Heart Disease, Haukeland University Hospital, N-5021 Bergen, Norway Submitted 17 May 2004 ; accepted in final form 8 July 2004 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/mm 2 and 0.95 ± 0.04 capillaries/fiber in sedentary control mice vs. 909 ± 55 capillaries/mm 2 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. adaptation; capillary density; endothelial cells; fiber type transformation; vascular endothelial growth factor Address for reprint requests and other correspondence: Z. Yan, Div. of Cardiology, Dept. of Medicine, Duke Univ. Medical Center, 4321 Medical Park Dr., Suite 200, Duke Univ. Independence Park Facility, Durham, NC 27704 (E-mail: zhen.yan{at}duke.edu )