BACKGROUND: 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. METHODS AND RESULTS: 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. CONCLUSIONS: We propose this procedure as a simple and practical method of therapeutic angiogenesis.
BACKGROUND: 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. METHODS AND RESULTS: 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. CONCLUSIONS: We propose this procedure as a simple and practical method of therapeutic angiogenesis.
Authors: Catherine C Kaczorowski; Timothy J Stodola; Brian R Hoffmann; Anthony R Prisco; Pengyuan Y Liu; Daniela N Didier; Jamie R Karcher; Mingyu Liang; Howard J Jacob; Andrew S Greene Journal: Physiol Genomics Date: 2013-09-10 Impact factor: 3.107
Authors: Ulrich Reinhart Goessler; Jens Stern-Straeter; Katrin Riedel; Gregor M Bran; Karl Hörmann; Frank Riedel Journal: Eur Arch Otorhinolaryngol Date: 2007-07-13 Impact factor: 2.503
Authors: Matthew Anderson; Namdev B Shelke; Ohan S Manoukian; Xiaojun Yu; Louise D McCullough; Sangamesh G Kumbar Journal: Crit Rev Biomed Eng Date: 2015
Authors: Gaurav Thakral; Paul J Kim; Javier LaFontaine; Robert Menzies; Bijan Najafi; Lawrence A Lavery Journal: J Diabetes Sci Technol Date: 2013-09-01
Authors: Bijan Najafi; Talal K Talal; Gurtej Singh Grewal; Robert Menzies; David G Armstrong; Lawrence A Lavery Journal: J Diabetes Sci Technol Date: 2017-02-01
Authors: E Bosi; M Conti; C Vermigli; G Cazzetta; E Peretti; M C Cordoni; G Galimberti; L Scionti Journal: Diabetologia Date: 2005-04-15 Impact factor: 10.122