Lundby Carsten, Pilegaard Henriette, Andersen Jesper L, van Hall Gerrit, Sander Mikael, Calbet Jose A L
The Copenhagen Muscle Research Centre at Rigshospitalet section 7652, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark.
J Exp Biol. 2004 Oct;207(Pt 22):3865-71. doi: 10.1242/jeb.01225.
Increased skeletal muscle capillary density would be a logical adaptive mechanism to chronic hypoxic exposure. However, animal studies have yielded conflicting results, and human studies are sparse. Neoformation of capillaries is dependent on endothelial growth factors such as vascular endothelial growth factor (VEGF), a known target gene for hypoxia inducible factor 1 (HIF-1). We hypothesised that prolonged exposure to high altitude increases muscle capillary density and that this can be explained by an enhanced HIF-1alpha expression inducing an increase in VEGF expression. We measured mRNA levels and capillary density in muscle biopsies from vastus lateralis obtained in sea level residents (SLR; N=8) before and after 2 and 8 weeks of exposure to 4100 m altitude and in Bolivian Aymara high-altitude natives exposed to approximately 4100 m altitude (HAN; N=7). The expression of HIF-1alpha or VEGF mRNA was not changed with prolonged hypoxic exposure in SLR, and both genes were similarly expressed in SLR and HAN. In SLR, whole body mass, mean muscle fibre area and capillary to muscle fibre ratio remained unchanged during acclimatization. The capillary to fibre ratio was lower in HAN than in SLR (2.4+/-0.1 vs 3.6+/-0.2; P<0.05). In conclusion, human muscle VEGF mRNA expression and capillary density are not significantly increased by 8 weeks of exposure to high altitude and are not increased in Aymara high-altitude natives compared with sea level residents.
骨骼肌毛细血管密度增加可能是对慢性低氧暴露的一种合理适应机制。然而，动物研究结果相互矛盾，而人体研究较少。毛细血管的新生依赖于内皮生长因子，如血管内皮生长因子（VEGF），它是缺氧诱导因子1（HIF-1）的一个已知靶基因。我们假设，长时间暴露于高海拔会增加肌肉毛细血管密度，这可以通过增强HIF-1α表达诱导VEGF表达增加来解释。我们测量了海平面居民（SLR；N = 8）在暴露于4100米海拔2周和8周之前及之后，以及玻利维亚艾马拉高海拔原住民（HAN；N = 7）暴露于约4100米海拔后，从股外侧肌获取的肌肉活检样本中的mRNA水平和毛细血管密度。在SLR中，长时间低氧暴露后HIF-1α或VEGF mRNA的表达没有变化，并且这两个基因在SLR和HAN中的表达相似。在SLR中，适应过程中全身质量、平均肌纤维面积和毛细血管与肌纤维的比例保持不变。HAN中的毛细血管与纤维比例低于SLR（2.4±0.1对3.6±0.2；P<0.05）。总之，暴露于高海拔8周后，人体肌肉VEGF mRNA表达和毛细血管密度没有显著增加，并且与海平面居民相比，艾马拉高海拔原住民也没有增加。
