Establishment of a Simple and Practical Procedure Applicable to Therapeutic Angiogenesis

Abstract

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. (Circulation.1999;99:2682-2687.)

Effect of sensory and motor electrical stimulation in vascular endothelial growth factor expression of muscle and skin in full-thickness wound

“…Evidence exists that electrical stimulation (ES) increases the release of VEGF in the muscle and wound site [7][8][9][10][11][12]. Thus, recruitment of muscle by ES may be a way to facilitate angiogenesis in wound healing.…”

“…In this study, the active electrode had negative polarity and was implanted onto the tibialis anterior muscle. In addition, some studies demonstrated that ES increased the release of VEGF in rat skeletal muscle, both when ES caused muscle contraction [10][11] and following subthreshold stimulation, which did not induce contraction [9]. Morris et al applied squarewave pulsed direct current (DC) ES to ischemic wounds in the ear of rabbits for either 1, 2, or 3 weeks (10 rabbits were assigned in two experimental groups, A and B) [12].…”

“…Evidence exists that ES increases the release of VEGF in muscle [7][8][9][10][11]. Hang et al reported that the VEGF gene expression is upregulated in rat skeletal muscle that was stimulated electrically at 10 Hz using 300 ms square waves at voltages that maximized contraction on palpation for up to 21 days [7].…”

“…In their study, the active electrode had negative polarity and was implanted onto the tibialis anterior muscle. Kanno et al reported that ES increased VEGF and blood flow when cultured skeletal muscle cells were electrically stimulated at a voltage that did not cause contraction [9].…”

The Effect of Wearing Shoes Generating Micro-currents on Body Composition and Blood Lipid Concentrations of Overweight Females

“…Since they are both similar to biocurrents, they have been effective at wound healing and in many studies. It has been reported that low electric stimulation is a promising approach to angiogenesis treatment 12,13) and that electric fields promote the secretion of growth factors 14) . In addition, micro-currents have been found to promote the switch of skin fibroblasts and U937 cells into growth factor-β1 (TGF-β1), an important regulator of inflammation and tissue regeneration 15) .…”