Establishment of a simple and practical procedure applicable to therapeutic angiogenesis

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 t...

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Veröffentlicht in:Circulation (New York, N.Y.) N.Y.), 1999-05, Vol.99 (20), p.2682-2687
Hauptverfasser: KANNO, S, ODA, N, ABE, M, SAITO, S, HORI, K, HANDA, Y, TABAYASHI, K, SATO, Y
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container_issue 20
container_start_page 2682
container_title Circulation (New York, N.Y.)
container_volume 99
creator KANNO, S
ODA, N
ABE, M
SAITO, S
HORI, K
HANDA, Y
TABAYASHI, K
SATO, Y
description 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.
doi_str_mv 10.1161/01.cir.99.20.2682
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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. 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Miscellaneous ; Electric Stimulation ; Endothelial Growth Factors - biosynthesis ; Endothelial Growth Factors - genetics ; Endothelial Growth Factors - metabolism ; Hindlimb - blood supply ; Ischemia - therapy ; Lymphokines - biosynthesis ; Lymphokines - genetics ; Lymphokines - metabolism ; Male ; Medical sciences ; Mice ; Muscle, Skeletal - cytology ; Muscle, Skeletal - metabolism ; Muscle, Smooth, Vascular - cytology ; Muscle, Smooth, Vascular - metabolism ; Neovascularization, Physiologic - physiology ; Rats ; Rats, Sprague-Dawley ; RNA, Messenger - metabolism ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors</subject><ispartof>Circulation (New York, N.Y.), 1999-05, Vol.99 (20), p.2682-2687</ispartof><rights>1999 INIST-CNRS</rights><rights>Copyright American Heart Association, Inc. 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Vascular system</topic><topic>Cell Line</topic><topic>Diseases of the peripheral vessels. Diseases of the vena cava. 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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.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams &amp; Wilkins</pub><pmid>10338463</pmid><doi>10.1161/01.cir.99.20.2682</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record>
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source MEDLINE; American Heart Association Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Journals@Ovid Complete
subjects Animals
Aorta - cytology
Aorta - metabolism
Biological and medical sciences
Blood and lymphatic vessels
Cardiology - methods
Cardiology. Vascular system
Cell Line
Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous
Electric Stimulation
Endothelial Growth Factors - biosynthesis
Endothelial Growth Factors - genetics
Endothelial Growth Factors - metabolism
Hindlimb - blood supply
Ischemia - therapy
Lymphokines - biosynthesis
Lymphokines - genetics
Lymphokines - metabolism
Male
Medical sciences
Mice
Muscle, Skeletal - cytology
Muscle, Skeletal - metabolism
Muscle, Smooth, Vascular - cytology
Muscle, Smooth, Vascular - metabolism
Neovascularization, Physiologic - physiology
Rats
Rats, Sprague-Dawley
RNA, Messenger - metabolism
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors
title Establishment of a simple and practical procedure applicable to therapeutic angiogenesis
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