Exercise-induced angiogenesis correlates with the up-regulated expression of neuronal nitric oxide synthase (nNOS) in human skeletal muscle
Exercise-induced angiogenesis correlates with the up-regulated expression of neuronal nitric oxide synthase (nNOS) in human skeletal muscle
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DOI：
10.1007/s00421-011-1960-x
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发表时间：
2012-01-01
影响因子：
3
通讯作者：
Baum, Oliver
中科院分区：
文献类型：
--
作者：
Huber-Abel, Felicitas A. M.;Gerber, Melanie;Baum, Oliver
耐力运动后神经元一氧化氮合酶（nNOS）对人体骨骼肌血管生成的贡献存在争议。因此，我们确定了 nNOS 的表达是否与股外侧肌 (VL) 肌肉活检中的毛细血管密度相关，该活检取自 10 名久坐的男性受试者，在适度训练之前和之后（每周 4 次每次 30 分钟的慢跑，持续 6 个月，心率相当于 75% VO(2)max）。在这些活检中，根据 RT-PCR 测定，nNOS 主要表达为具有外显子 mu 的 α 同工型，并且在较小程度上表达不具有外显子 mu 的 nNOS。 nNOS 的 mRNA 水平通过实时 PCR 进行定量，并与毛细血管与纤维的比率以及光学显微镜下指定的毛细血管的数值密度相关。如果对所有受试者的 VL 活检进行共同分析，训练后 nNOS 的 mRNA 水平没有显着升高（+34%；P > 0.05）。然而，十名受试者中只有五名表现出毛细血管与纤维比率（+ 25％）和毛细血管数量密度（+ 21％）显着升高（P为千分之0.05），因此正在经历血管生成。如果单独评估这 5 名受试者的 VL 活检，则 nNOS 的 mRNA 水平显着上调（+128%；P 千分之一货币符号 0.05），并与血管生成呈正相关（r = 0.8；P 千分之一货币符号 0.01）。因此，仅在那些经历血管生成的受试者中，通过免疫印迹定量的 VL 活检中的 nNOS 蛋白表达显着增加（+82%；P 千分之一货币符号 0.05）。总之，nNOS 在 mRNA 和蛋白质水平上的表达与运动后的毛细血管有统计相关性，表明 nNOS 参与了人类骨骼肌对训练的血管生成反应。
The contribution of neuronal nitric oxide synthase (nNOS) to angiogenesis in human skeletal muscle after endurance exercise is controversially discussed. We therefore ascertained whether the expression of nNOS is associated with the capillary density in biopsies of the vastus lateralis (VL) muscle that had been derived from 10 sedentary male subjects before and after moderate training (four 30-min weekly jogging sessions for 6 months, with a heart-rate corresponding to 75% VO(2)max). In these biopsies, nNOS was predominantly expressed as alpha-isoform with exon-mu and to a lesser extent without exon-mu, as determined by RT-PCR. The mRNA levels of nNOS were quantified by real-time PCR and related to the capillary-to-fibre ratio and the numerical density of capillaries specified by light microscopy. If the VL biopsies of all subjects were co-analysed, mRNA levels of nNOS were non-significantly elevated after training (+34%; P > 0.05). However, only five of the ten subjects exhibited significant (P a parts per thousand currency sign 0.05) elevations in the capillary-to-fibre ratio (+25%) and the numerical density of capillaries (+21%) and were thus undergoing angiogenesis. If the VL biopsies of these five subjects alone were evaluated, the mRNA levels of nNOS were significantly up-regulated (+128%; P a parts per thousand currency sign 0.05) and correlated positively (r = 0.8; P a parts per thousand currency sign 0.01) to angiogenesis. Accordingly, nNOS protein expression in VL biopsies quantified by immunoblotting was significantly increased (+82%; P a parts per thousand currency sign 0.05) only in those subjects that underwent angiogenesis. In conclusion, the expression of nNOS at mRNA and protein levels was statistically linked to capillarity after exercise suggesting that nNOS is involved in the angiogenic response to training in human skeletal muscle.