Valdivieso Paola, Toigo Marco, Hoppeler Hans, Flück Martin
Laboratory for Muscle Plasticity, Department of Orthopedics, University of Zurich, Balgrist Campus, Zurich, Switzerland.
Institute of Anatomy, University of Berne, Berne, Switzerland.
PLoS One. 2017 Apr 6;12(4):e0174864. doi: 10.1371/journal.pone.0174864. eCollection 2017.
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.
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).
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.
Our findings provide evidence for a negative influence of T/T homozygosity in rs2104772 on capillary remodeling with endurance exercise.
机械应力，包括与血压相关的因素，可上调骨骼肌中促血管生成的细胞外基质蛋白腱生蛋白-C的表达。我们推测，耐力训练期间随着灌注反复增加，骨骼肌毛细血管化增加与腱生蛋白-C的血管相关表达有关，并且会受到单核苷酸多态性（SNP）rs2104772的影响，该多态性特征为腱生蛋白-C氨基酸密码子1677中的胸腺嘧啶（T）到腺嘌呤（A）的非同义交换。
61名健康、未经训练、具有瑞士血统的男性白人参与者在连续工作日使用自行车测力计进行30次30分钟的耐力运动。在经Bonferroni校正的5% p值（重复测量方差分析）下，基因型与训练的相互作用被认为具有显著性。
耐力训练使股外侧肌的毛细血管与纤维比率增加了11%，毛细血管密度增加了7%，线粒体体积密度增加了30%。该肌肉中腱生蛋白-C的蛋白表达局限于小动脉和小静脉（80%的病例），并且在A等位基因携带者训练后增加。训练前，股外侧肌肌膜下和肌原纤维线粒体的体积密度在A/A纯合子中分别比T核苷酸携带者（A/T和T/T）高49%和18%。训练特别增加了A核苷酸携带者的毛细血管与纤维比率，但在T/T纯合子中没有增加。运动后8种血管生成相关转录本的表达反应反映了血管生成的基因型特异性调节，并通过训练诱导的剪切应力相关因子波形蛋白和血管内皮生长因子A的改变得到证实。
我们的研究结果为rs2104772中T/T纯合性对耐力运动时毛细血管重塑的负面影响提供了证据。
