Capillary regression in vascular endothelial growth factor-deficient skeletal muscle
Capillary regression in vascular endothelial growth factor-deficient skeletal muscle
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DOI：
10.1152/physiolgenomics.00023.2004
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发表时间：
2004-06-17
影响因子：
4.6
通讯作者：
Wagner, PD
中科院分区：
文献类型：
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作者：
Tang, K;Breen, EC;Wagner, PD
骨骼肌血管生成是对代谢需求增加的重要生理适应，可能依赖于血管内皮生长因子（VEGF），其表达增加是已知的对运动的早期反应。为了验证VEGF对肌肉毛细血管维持至关重要的假设，我们评估了出生后笼内VEGFloxP（+/+）小鼠靶向骨骼肌抑制VEGF表达的后果。为了删除VEGF，使用重组腺相关cre重组酶表达病毒载体的直接肌内注射完成cre重组酶表达。感染后4周，VEGF失活区域显示毛细血管密度和毛细血管与纤维比率下降64%。在VEGF缺失区也观察到大量凋亡。在第8周没有证据显示有补救作用，毛细血管与纤维比率持续下降67%，毛细血管密度下降69%。这些数据暗示VEGF作为肌肉毛细作用的基本存活因子，并且还证明VEGF依赖性信号传导不足导致小鼠骨骼肌细胞凋亡。
Skeletal muscle angiogenesis is an important physiological adaptation to increased metabolic demand, possibly dependent on vascular endothelial growth factor ( VEGF), the increased expression of which is a known early response to exercise. To test the hypothesis that VEGF is essential to muscle capillary maintenance, we evaluated the consequences of targeted skeletal muscle inhibition of VEGF expression in postnatal, cage-confined VEGFloxP(+/+) mice. To delete VEGF, cre recombinase expression was accomplished using direct intramuscular injection of a recombinant adeno-associated cre recombinase expressing viral vector. Four weeks postinfection, VEGF-inactivated regions revealed 64% decreases in capillary density and capillary-to-fiber ratio. Substantial apoptosis was also observed in VEGF-depleted regions. There was no evidence of rescue at 8 wk, with a persistent 67% reduction in capillary-to-fiber ratio and a 69% decrease in capillary density. These data implicate VEGF as an essential survival factor for muscle capillarity and also demonstrate insufficient VEGF-dependent signaling leads to apoptosis in mouse skeletal muscle.