Angiogenesis induced by electrical stimulation is mediated by angiotensin II and VEGF

Angiogenesis induced by electrical stimulation is mediated by angiotensin II and VEGF
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DOI:
10.1038/sj.mn.7300142
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发表时间:
2001-02-01
期刊:
影响因子:
2.4
通讯作者:
Greene, AS
Greene, AS
中科院分区:
医学4区
文献类型:
--
作者:
Amaral, SL;Linderman, JR;Greene, AS

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目的:骨骼肌生理性血管生成是对运动训练和电刺激的适应性反应。研究血管紧张素II(Ang II)在电刺激诱导血管生成和血管内皮生长因子(VEGF)蛋白表达中的作用。方法:SD大鼠右侧胫前肌(Th)和趾长伸肌(EDL)每天刺激8h,连续7d。对侧肌作为对照。手术前两天和整个刺激方案。这些大鼠在饮用水中加入赖诺普利或氯沙坦。以未经任何药物治疗的大鼠为对照。用免疫组织化学和Western印迹分析鉴定酸性蛋白的反定量!血管内皮生长因子蛋白在这些肌肉中的表达。结果:慢性电刺激骨骼肌后7d内血管密度显著增加(EDL和TA分别为14%和30%)。此外,刺激增加了刺激肌肉中血管内皮生长因子的蛋白水平。赖诺普利和氯沙坦均阻断血管内皮生长因子的表达,抑制刺激诱导的血管生成。结论:血管紧张素II受体(AT(1))和血管内皮生长因子(VEGF)参与了电刺激血管生成的信号转导途径。
Objective: Physiological angiogenesis in skeletal muscle is an adaptive response to physical training and electrical stimulation. This study investigated the role of angiotensin II (Ang II) in regulating both angiogenesis and vascular endothelial growth factor (VEGF) protein Expression induced by electrical stimulation.Methods: The right tibialis anterior (Th) and extensor digitorum longus (EDL) muscles of Sprague-Dawley rats were stimulated for 8 hours per day for 7 days. The contralateral muscles served as controls. Two days before the surgery and throughout the stimulation protocol. the rats received either lisinopril or losartan in their drinking water. Rats without any drug treatment were used as control. Immunohistochemistry and Western blot analysis were performed to identify the sour ce anti quantify! the VEGF protein expression in these muscles. The relationship between angiogenesis and VEGF expression was explored using a VEGF-neutralizing antibody.Results: Chronic electrical stimulation of the skeletal muscles led to significant increases in vessel density (14% and 30% for EDL and TA, respectively) within 7 days. In addition: stimulation increased VEGF protein levels in the stimulated muscles. Both lisinopril and losartan blocked elevation in VEGF expression and inhibited the angiogenesis induced by stimulation. VEGF neutralization also inhibited angiogenesis, confirming the relationship between Ang II: VEGF, and vessel growth.Conclusion: The current study suggests a pathway involving angiotensin II receptors (AT(1)) and VEGF in electrically stimulated angiogenesis.