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1 Medicine, Duke University Medical Center, Durham, NC, USA
2 Heart Disease, Haukeland University Hospital, Bergen, Norway
3 Medicine, Duke University Medical Center, Durham, NC, USA; Medicine, Durham Veterans Administration, Durham, NC, USA
* To whom correspondence should be addressed. E-mail: zhen.yan{at}duke.edu.
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 the spatial changes in fiber type composition and capillary density in a mouse model of endurance training. Long-term voluntary running (4 weeks) in C57BL/6 mice resulted in a ~2-fold 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/mm2 and 0.95 ± 0.04 capillaries/fiber in the sedentary control mice vs. 909 ± 55 and 1.70 ± 0.04 in the 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, prior to 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 showed that the increase in capillary contacting was 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.
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