Kanno S, Oda N, Abe M, Saito S, Hori K, Handa Y, Tabayashi K, Sato Y
Department of Vascular Biology, Institute of Development, Aging, and Cancer, Tohoku University, Sendai, Japan.
Circulation. 1999 May 25;99(20):2682-7. doi: 10.1161/01.cir.99.20.2682.
Therapeutic angiogenesis is thought to be beneficial for serious ischemic diseases. This investigation was designed to establish a simple and practical procedure applicable to therapeutic angiogenesis.
When cultured skeletal muscle cells were electrically stimulated at a voltage that did not cause their contraction, vascular endothelial growth factor (VEGF) mRNA was augmented at an optimal-frequency stimulation. This increase of VEGF mRNA was derived primarily from transcriptional activation. Electrical stimulation increased the secretion of VEGF protein into the medium. This conditioned medium then augmented the growth of endothelial cells. The effect of electrical stimulation was further confirmed in a rat model of hindlimb ischemia. The tibialis anterior muscle in the ischemic limb was electrically stimulated. The frequency of stimulation was 50 Hz and strength was 0.1 V, which was far below the threshold for muscle contraction. After a 5-day stimulation, there was a significant increase in blood flow within the muscle. Immunohistochemical analysis revealed that VEGF protein was synthesized and capillary density was significantly increased in the stimulated muscle. Rats tolerated this procedure very well, and there was no muscle contraction, muscle injury, or restriction in movement.
We propose this procedure as a simple and practical method of therapeutic angiogenesis.
治疗性血管生成被认为对严重缺血性疾病有益。本研究旨在建立一种适用于治疗性血管生成的简单实用方法。
当培养的骨骼肌细胞在不会引起其收缩的电压下进行电刺激时，血管内皮生长因子（VEGF）mRNA在最佳频率刺激下增加。VEGF mRNA的这种增加主要源于转录激活。电刺激增加了VEGF蛋白向培养基中的分泌。这种条件培养基随后促进了内皮细胞的生长。电刺激的效果在大鼠后肢缺血模型中得到进一步证实。对缺血肢体的胫前肌进行电刺激。刺激频率为50Hz，强度为0.1V，远低于肌肉收缩阈值。经过5天的刺激后，肌肉内血流量显著增加。免疫组织化学分析显示，刺激肌肉中合成了VEGF蛋白，毛细血管密度显著增加。大鼠对该方法耐受性良好，未出现肌肉收缩、肌肉损伤或运动受限。
我们提出该方法是一种简单实用的治疗性血管生成方法。
