VEGF gene expression is upregulated in electrically stimulated rat skeletal muscle

Abstract

Vascular endothelial growth factor (VEGF; also called vascular permeability factor) is a secreted mitogen with distinct target cell specificity for vascular endothelial cells. Hypoxia upregulates VEGF expression, making it a likely mediator of the angiogenesis that occurs in poorly perfused tissues. The purpose of this study was to determine whether VEGF gene expression is upregulated in chronically stimulated skeletal muscles, where hypoxia is thought to trigger the growth of blood vessels. The right anterior tibialis and extensor digitorum longus muscles of 12 rats were stimulated electrically (10 Hz, 300 microseconds pulses) for up to 21 days by way of the peroneal motor nerve. The contralateral muscles served as control. Northern analysis showed that VEGF mRNA levels increased by approximately sixfold after 4 days of stimulation and then decreased gradually over the next several days. VEGF mRNA levels were still elevated by two- to threefold after 21 days of stimulation. Higher VEGF mRNA levels in the early stages of muscle stimulation and gradually decreasing levels in later stages are consistent with a metabolic hypothesis in which tissue oxygenation controls VEGF expression. These studies support the hypothesis that VEGF has a physiological role in promoting angiogenesis in stimulated skeletal muscle.

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.…”

“…Thus, recruitment of muscle by ES may be a way to facilitate angiogenesis in wound healing. Hang et al reported the VEGF gene expression is unregulated in rat skeletal muscle [7]. They stimulated muscle electrically at 10 Hz using 300 ms square waves at voltages that maximized contraction on palpation for up to 21 days.…”

“…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].…”

“…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]. Nagasaka et al reported that the VEGF protein was significantly increased by LVES in rat skeletal muscle that was stimulated continuously for 5 days at 50 Hz, with unipolar square waves at stimulus strength below threshold muscle contraction [8].…”

Diaphragmatic angiogenic growth factor mRNA responses to increased ventilation caused by hypoxia and hypercapnia

“…In addition, electrical stimulation increases VEGF levels [10]. Recently, it was demonstrated that passively-induced hyperperfusion does not increase muscle VEGF mRNA, and it was speculated that either intracellular hypoxia or mechanical effects of contraction per se (such as ®bre stretch) may be responsible for this increase [11].…”