Expression of angiogenic regulators and skeletal muscle capillarity in selectively bred high aerobic capacity mice
Expression of angiogenic regulators and skeletal muscle capillarity in selectively bred high aerobic capacity mice
复制标题
选择性饲养的高有氧能力小鼠血管生成调节因子和骨骼肌毛细血管的表达
作者：
Gerald N. Audet;Thomas H. Meek;T. Garland, Jr.;I. Olfert
在未经训练的小鼠中选择性繁殖高自愿轮跑步导致了“迷你肌肉”（MM）表型，与来自非选择对照系的肌肉相比，其增加了骨骼肌毛细血管。血管内皮生长因子（VEGF）和血小板反应蛋白-1（TSP-1）是骨骼肌血管生成的重要介质;因此，我们假设肌肉毛细血管增加的未经训练的MM小鼠的基础VEGF表达较高，基础TSP-1表达较低，并且可能对急性运动产生过度的VEGF反应。我们检查了两种（未经训练的）选择性饲养的高运动能力小鼠品系（MM和非MM）以及一种非选择的对照小鼠品系（正常有氧能力）雄性小鼠的骨骼肌形态和VEGF和TSP-1的骨骼肌蛋白表达。在MM小鼠中，腓肠肌（GA）和跖肌（PLT）肌肉毛细血管（即毛细血管与纤维比和毛细血管密度）比对照小鼠更大（P <0.05）。在非MM小鼠中，仅PLT中的肌肉毛细血管大于对照小鼠（P <0.001）。 比目鱼肌（SOL）的肌毛细作用组间无统计学差异。在GA中，MM小鼠的基础VEGF增加了58%（P <0.05），与对照小鼠相比，基础TSP-1无统计学差异。 在PLT中，与对照动物相比，MM小鼠的基础VEGF增加79%（P <0.05），基础TSP-1降低39%（P <0.05）。 与对照小鼠相比，非MM小鼠在GA或PLT中的基础VEGF无差异。相比之下，与对照小鼠相比，非MM小鼠的PLT中基础TSP-1升高，但GA中未升高。在三种小鼠品系中，SOL肌肉中VEGF和TSP-1均无显著差异。在对急性运动的反应中，MM小鼠在GA和PLT中分别显示出41%和28%的VEGF增加（P <0.05），而对照和非MM小鼠均未显示出对急性运动的显著VEGF反应。 相比之下，在MM小鼠中，响应于急性运动，GA中的TSP-1水平降低了90%（P <0.05），但PLT中增加了50%（P <0.05）。 SOL显示任何小鼠系的VEGF或TSP-1对运动均无应答。除非MM跖肌外，这些数据表明毛细血管增加与阳性和阴性血管生成调节因子（即分别为VEGF和TSP-1）之间的平衡改变相关。 基于MM小鼠中更大的毛细血管和对运动的显著VEGF反应，这些数据表明VEGF表达可能至少部分由遗传决定。
Selective breeding for high voluntary wheel running in untrained mice has resulted in a ‘mini muscle’ (MM) phenotype, which has increased skeletal muscle capillarity compared with muscles from non‐selected control lines. Vascular endothelial growth factor (VEGF) and thrombospondin‐1 (TSP‐1) are essential mediators of skeletal muscle angiogenesis; thus, we hypothesized that untrained MM mice with elevated muscle capillarity would have higher basal VEGF expression and lower basal TSP‐1 expression, and potentially an exaggerated VEGF response to acute exercise. We examined skeletal muscle morphology and skeletal muscle protein expression of VEGF and TSP‐1 in male mice from two (untrained) mouse lines selectively bred for high exercise capacity (MM and Non‐MM), as well as one non‐selected control mouse line (normal aerobic capacity). In the MM mice, gastrocnemius (GA) and plantaris (PLT) muscle capillarity (i.e. capillary‐to‐fibre ratio and capillary density) were greater compared with control mice (P < 0.05). In Non‐MM mice, only muscle capillarity in PLT was greater than in control mice (P < 0.001). The soleus (SOL) showed no statistical differences in muscle capillarity among groups. In the GA, MM mice had 58% greater basal VEGF (P < 0.05), with no statistical difference in basal TSP‐1 when compared with control mice. In the PLT, MM mice had a 79% increase in basal VEGF (P < 0.05) and a 39% lower basal TSP‐1 (P < 0.05) compared with the control animals. Non‐MM mice showed no difference in basal VEGF in either the GA or the PLT compared with control mice. In contrast, basal TSP‐1 was elevated in the PLT, but not in the GA, of Non‐MM mice compared with control mice. Neither VEGF nor TSP‐1 was significantly different in SOL muscle among the three mouse lines. In response to acute exercise, MM mice displayed a 41 and 28% increase (P < 0.05) in VEGF in the GA and PLT, respectively, whereas neither control nor Non‐MM mice showed a significant VEGF response to acute exercise. In contrast, TSP‐1 levels were decreased by 90% in GA (P < 0.05) but increased by 50% in PLT (P < 0.05) in response to acute exercise in MM mice. The SOL showed no response to exercise for either VEGF or TSP‐1 for any of the mouse lines. These data, with the exception of the Non‐MM plantaris muscle, suggest that elevated capillarity is associated with altered balance between positive and negative angiogenic regulators (i.e. VEGF versus TSP‐1, respectively). Based on the greater capillarity and significant VEGF response to exercise in MM mice, these data suggest that VEGF expression may, at least in part, be genetically determined.
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DOI：
10.1152/ajpregu.00347.2010
发表时间：
2010-10-01
影响因子：
2.8
作者：
Olfert, I. Mark;Howlett, Richard A.;Breen, Ellen C.
通讯作者：
Breen, Ellen C.
DOI：
10.1152/ajpheart.1999.277.6.h2247
发表时间：
1999-12-01
影响因子：
4.8
作者：
Richardson, RS;Wagner, H;Wagner, PD
通讯作者：
Wagner, PD
影响因子：
4.6
作者：
Tang, K;Breen, EC;Wagner, PD
通讯作者：
Wagner, PD
有氧能力近交大鼠模型心血管调节的表型差异。
DOI：
10.1152/physiolgenomics.1999.1.2.63
发表时间：
1999
期刊：
Physiological genomics.
影响因子：
--
作者：
Koch,LG;Britton,SL;Barbato,JC;Rodenbaugh,DW;DiCarlo,SE
通讯作者：
DiCarlo,SE
影响因子：
4.6
作者：
Koch, LG;Britton, SL
通讯作者：
Britton, SL