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(Circulation. 1999;99:2682-2687.)
© 1999 American Heart Association, Inc.

Basic Science Reports

Establishment of a Simple and Practical Procedure Applicable to Therapeutic Angiogenesis

Shinichi Kanno, MD; Nobuyuki Oda, MSc; Mayumi Abe, MD, PhD; Sachiko Saito, PhD; Katsuyoshi Hori, PhD; Yasunobu Handa, MD, PhD; Koichi Tabayashi, MD, PhD; Yasufumi Sato, MD, PhD

From the Department of Vascular Biology, Institute of Development, Aging, and Cancer, Tohoku University (S.K., N.O., M.A., S.S., K.H., Y.S.); the Department of Restorative Neuromuscular Surgery and Rehabilitation, Tohoku University Graduate School of Medicine (Y.H.); and the Department of Thoracic and Cardiovascular Surgery, Tohoku University School of Medicine (S.K., K.T.), Sendai, Japan.

Correspondence to Yasufumi Sato, MD, PhD, Department of Vascular Biology, Institute of Development, Aging, and Cancer, Tohoku University, 4-1 Seiryomachi, Aoba-ku, Sendai, 980-8575, Japan. E-mail y-sato{at}idac.tohoku.ac.jp

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.

Key Words: electrical stimulation • growth substances • angiogenesis

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