title: Pro- and anti-angiogenic factors in human skeletal muscle in response to acute exercise and training.
abstract: This study examined the effect of acute exercise and 4 weeks of aerobic training on skeletal muscle gene and protein expression of pro- and anti-angiogenic factors in 14 young male subjects. Training consisted of 60 min of cycling (∼60% of ), 3 times/week. Biopsies were obtained from vastus lateralis muscle before and after training. Muscle interstitial fluid was collected during cycling at weeks 0 and 4. Training increased (P < 0.05) the capillary: fibre ratio and capillary density by 23% and 12%, respectively. The concentration of interstitial vascular endothelial growth factor (VEGF) in response to acute exercise increased similarly (>6-fold; P < 0.05) before and after training. Resting protein levels of soluble VEGF receptor-1 in interstitial fluid, and of VEGF, thrombospondin-1 (TSP-1) and tissue inhibitor of matrix metalloproteinase-1 (TIMP1) in muscle were unaffected by training, whereas endothelial nitric oxide synthase protein levels in muscle increased by 50% (P < 0.05). Before and after training, acute exercise induced a similar increase (P < 0.05) in the mRNA level of angiopoietin 2, matrix metalloproteinase 9 and TSP-1. After training, TIMP1 mRNA content increased with exercise (P < 0.05). In conclusion, acute exercise induced a similar increase in the gene-expression of both pro- and anti-angiogenic factors in untrained and trained muscle. We propose that the increase in anti-angiogenic factors with exercise is important for modulation of angiogenesis. The lack of effect of training on basal muscle VEGF protein levels and VEGF secretion during exercise suggests that increased VEGF levels are not a prerequisite for exercise-induced capillary growth in healthy muscle.
authors.affiliation: Department of Exercise and Sport Sciences, University of Copenhagen, Universitetsparken 13, DK-2100 Copenhagen, Denmark.
authors.forename: B
authors.initials: B
authors.lastname: Hoier
authors.forename: N
authors.initials: N
authors.lastname: Nordsborg
authors.forename: S
authors.initials: S
authors.lastname: Andersen
authors.forename: L
authors.initials: L
authors.lastname: Jensen
authors.forename: L
authors.initials: L
authors.lastname: Nybo
authors.forename: J
authors.initials: J
authors.lastname: Bangsbo
authors.forename: Y
authors.initials: Y
authors.lastname: Hellsten
mesh_terms: D000328:Adult; D043925:Angiogenesis Inducing Agents / Q000378:metabolism; D020533:Angiogenesis Inhibitors / Q000378:metabolism; D042683:Angiopoietin-1 / Q000235:genetics; D042702:Angiopoietin-2 / Q000235:genetics; D049109:Cell Proliferation; D015444:Exercise / Q000502:physiology*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D018482:Muscle, Skeletal / Q000502:physiology*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D042787:Receptor, TIE-2 / Q000235:genetics; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism; D019700:Thrombospondin 1 / Q000235:genetics / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: C467630:ANGPT1 protein, human; D043925:Angiogenesis Inducing Agents; D020533:Angiogenesis Inhibitors; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D012333:RNA, Messenger; D019700:Thrombospondin 1; D019715:Tissue Inhibitor of Metalloproteinase-1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042787:Receptor, TIE-2; D040262:Receptors, Vascular Endothelial Growth Factor; D020780:Matrix Metalloproteinase 9