Human VEGF gene expression in skeletal muscle: effect of acute normoxic and hypoxic exercise
Human VEGF gene expression in skeletal muscle: effect of acute normoxic and hypoxic exercise
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DOI：
10.1152/ajpheart.1999.277.6.h2247
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发表时间：
1999-12-01
影响因子：
4.8
通讯作者：
Wagner, PD
中科院分区：
文献类型：
--
作者：
Richardson, RS;Wagner, H;Wagner, PD
血管内皮生长因子（Vascular endothelial growth factor， VEGF）参与细胞外基质的改变和内皮细胞的增殖，这两者都是新毛细血管生长的前体。血管生成是对运动训练的重要适应，运动诱导的细胞内Po-2的减少被认为是这一过程的刺激因素。因此，我们研究了在常氧和缺氧（12% O-2）条件下运动时肌肉细胞Po-2[肌红蛋白Po-2 (MbPo(2))]，并通过定量Northern分析研究了6名未训练受试者单次运动后VEGF的mRNA水平。单腿膝盖伸展提供了急性运动刺激：在这个分级测试中，以达到峰值工作速率的50%进行最大测试，然后进行30分钟。由于峰值工作速率不受缺氧的影响，因此在缺氧和常氧条件下，绝对和相对工作速率是相同的。取股外侧肌皮周穿刺活检3例，静息时1例，运动后1 h常氧或缺氧时1例。在休息时（对照组），VEGF mRNA水平非常低（0.38 +/- 0.04 VEGF/18S）。在常氧或缺氧条件下运动后，VEGF mRNA水平明显升高（分别为16.9 +/- 6.7或7.1 +/- 1.8 VEGF/18S）。相比之下，在运动后1小时，没有可测量的碱性成纤维细胞生长因子mRNA对运动的反应。肌红蛋白磁共振波谱证实，与正常缺氧（7.2 +/- 0.6 mmHg）相比，缺氧时MbPo(2) （3.8 +/- 0.3 mmHg）降低，但未能揭示运动时MbPo(2)与VEGF表达之间的关系。急性运动反应中VEGF mRNA的增加支持了VEGF参与运动诱导的骨骼肌血管生成的概念，但质疑细胞Po-2减少作为这种反应刺激的重要性。
Vascular endothelial growth factor (VEGF) is involved in extracellular matrix changes and endothelial cell proliferation, both of which are precursors to new capillary growth. Angiogenesis is a vital adaptation to exercise training, and the exercise-induced reduction in intracellular Po-2 has been proposed as a stimulus for this process. Thus we studied muscle cell Po-2 [myoglobin Po-2 (MbPo(2))] during exercise in normoxia and in hypoxia (12% O-2) and studied the mRNA levels of VEGF in six untrained subjects after a single bout of exercise by quantitative Northern analysis. Single-leg knee extension provided the acute exercise stimulus: a maximal test followed by 30 min at 50% of the peak work rate achieved in this graded test. Because peak work rate was not affected by hypoxia, the absolute and relative work rates were identical in hypoxia and normoxia. Three pericutaneous needle biopsies were collected from the vastus lateralis muscle, one at rest and then the others at 1 h after exercise in normoxia or hypoxia. At rest (control), VEGF mRNA levels were very low (0.38 +/- 0.04 VEGF/18S). After exercise in normoxia or hypoxia, VEGF mRNA levels were much greater (16.9 +/- 6.7 or 7.1 +/- 1.8 VEGF/18S, respectively). In contrast, there was no measurable basic fibroblast growth factor mRNA response to exercise at this 1-h postexercise time point. Magnetic resonance spectroscopy of myoglobin confirmed a reduction in MbPo(2) in hypoxia (3.8 +/- 0.3 mmHg) compared with normoxia (7.2 +/- 0.6 mmHg) but failed to reveal a relationship between MbPo(2) during exercise and VEGF expression. This VEGF mRNA increase in response to acute exercise supports the concept that VEGF is involved in exercise-induced skeletal muscle angiogenesis but questions the importance of a reduced cellular Po-2 as a stimulus for this response.