title: T/T homozygosity of the tenascin-C gene polymorphism rs2104772 negatively influences exercise-induced angiogenesis.
abstract: BACKGROUND
  Mechanical stress, including blood pressure related factors, up-regulate expression of the pro-angiogenic extracellular matrix protein tenascin-C in skeletal muscle. We hypothesized that increased capillarization of skeletal muscle with the repeated augmentation in perfusion during endurance training is associated with blood vessel-related expression of tenascin-C and would be affected by the single-nucleotide polymorphism (SNP) rs2104772, which characterizes the non-synonymous exchange of thymidine (T)-to-adenosine (A) in the amino acid codon 1677 of tenascin-C.
  
  
  METHODS
  Sixty-one healthy, untrained, male white participants of Swiss descent performed thirty 30-min bouts of endurance exercise on consecutive weekdays using a cycling ergometer. Genotype and training interactions were called significant at Bonferroni-corrected p-value of 5% (repeated measures ANOVA).
  
  
  RESULTS
  Endurance training increased capillary-to-fiber-ratio (+11%), capillary density (+7%), and mitochondrial volume density (+30%) in m. vastus lateralis. Tenascin-C protein expression in this muscle was confined to arterioles and venules (80% of cases) and increased after training in A-allele carriers. Prior to training, volume densities of subsarcolemmal and myofibrillar mitochondria in m. vastus lateralis muscle were 49% and 18%, respectively, higher in A/A homozygotes relative to T-nucleotide carriers (A/T and T/T). Training specifically increased capillary-to-fiber ratio in A-nucleotide carriers but not in T/T homozygotes. Genotype specific regulation of angiogenesis was reflected by the expression response of 8 angiogenesis-associated transcripts after exercise, and confirmed by training-induced alterations of the shear stress related factors, vimentin and VEGF A.
  
  
  CONCLUSIONS
  Our findings provide evidence for a negative influence of T/T homozygosity in rs2104772 on capillary remodeling with endurance exercise.
authors.affiliation: Laboratory for Muscle Plasticity, Department of Orthopedics, University of Zurich, Balgrist Campus, Zurich, Switzerland.
authors.forename: Paola
authors.identifier: http://orcid.org/0000-0001-9322-4510
authors.initials: P
authors.lastname: Valdivieso
authors.affiliation: Laboratory for Muscle Plasticity, Department of Orthopedics, University of Zurich, Balgrist Campus, Zurich, Switzerland.
authors.forename: Marco
authors.initials: M
authors.lastname: Toigo
authors.affiliation: Institute of Anatomy, University of Berne, Berne, Switzerland.
authors.forename: Hans
authors.initials: H
authors.lastname: Hoppeler
authors.affiliation: Laboratory for Muscle Plasticity, Department of Orthopedics, University of Zurich, Balgrist Campus, Zurich, Switzerland.|Institute of Anatomy, University of Berne, Berne, Switzerland.
authors.forename: Martin
authors.identifier: http://orcid.org/0000-0002-0479-7243
authors.initials: M
authors.lastname: Flück
mesh_terms: D000241:Adenosine / Q000235:genetics; D000328:Adult; D001706:Biopsy; D015444:Exercise; D006720:Homozygote; D006801:Humans; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply; D018919:Neovascularization, Physiologic / Q000235:genetics* / Q000502:physiology; D010807:Physical Endurance; D020641:Polymorphism, Single Nucleotide; D019063:Tenascin / Q000737:chemistry / Q000235:genetics*; D013936:Thymidine / Q000235:genetics; D055815:Young Adult
chemical_list: D019063:Tenascin; D000241:Adenosine; D013936:Thymidine