Low energy shock wave therapy induces angiogenesis in acute hind-limb ischemia via VEGF receptor 2 phosphorylation

Low energy shock waves have been shown to induce angiogenesis, improve left ventricular ejection fraction and decrease angina symptoms in patients suffering from chronic ischemic heart disease. Whether there is as well an effect in acute ischemia was not yet investigated. Hind-limb ischemia was indu...

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Veröffentlicht in:PloS one 2014-08, Vol.9 (8), p.e103982-e103982
Hauptverfasser: Holfeld, Johannes, Tepeköylü, Can, Blunder, Stefan, Lobenwein, Daniela, Kirchmair, Elke, Dietl, Marion, Kozaryn, Radoslaw, Lener, Daniela, Theurl, Markus, Paulus, Patrick, Kirchmair, Rudolf, Grimm, Michael
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container_issue 8
container_start_page e103982
container_title PloS one
container_volume 9
creator Holfeld, Johannes
Tepeköylü, Can
Blunder, Stefan
Lobenwein, Daniela
Kirchmair, Elke
Dietl, Marion
Kozaryn, Radoslaw
Lener, Daniela
Theurl, Markus
Paulus, Patrick
Kirchmair, Rudolf
Grimm, Michael
description Low energy shock waves have been shown to induce angiogenesis, improve left ventricular ejection fraction and decrease angina symptoms in patients suffering from chronic ischemic heart disease. Whether there is as well an effect in acute ischemia was not yet investigated. Hind-limb ischemia was induced in 10-12 weeks old male C57/Bl6 wild-type mice by excision of the left femoral artery. Animals were randomly divided in a treatment group (SWT, 300 shock waves at 0.1 mJ/mm2, 5 Hz) and untreated controls (CTR), n = 10 per group. The treatment group received shock wave therapy immediately after surgery. Higher gene expression and protein levels of angiogenic factors VEGF-A and PlGF, as well as their receptors Flt-1 and KDR have been found. This resulted in significantly more vessels per high-power field in SWT compared to controls. Improvement of blood perfusion in treatment animals was confirmed by laser Doppler perfusion imaging. Receptor tyrosine kinase profiler revealed significant phosphorylation of VEGF receptor 2 as an underlying mechanism of action. The effect of VEGF signaling was abolished upon incubation with a VEGFR2 inhibitor indicating that the effect is indeed VEGFR 2 dependent. Low energy shock wave treatment induces angiogenesis in acute ischemia via VEGF receptor 2 stimulation and shows the same promising effects as known from chronic myocardial ischemia. It may therefore develop as an adjunct to the treatment armentarium of acute muscle ischemia in limbs and myocardium.
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subjects Acute Disease
Angina
Angiogenesis
Animals
Biology and life sciences
Blood vessels
Cardiology
Cardiovascular disease
Cardiovascular diseases
Coronary artery disease
Coronary vessels
Doppler effect
Energy
Femoral artery
Femur
Gene expression
Gene therapy
Heart
Heart attacks
Heart diseases
Heart surgery
High-Energy Shock Waves - therapeutic use
Hindlimb - blood supply
Hindlimb - radiation effects
Hospitals
Internal medicine
Ischemia
Ischemia - metabolism
Ischemia - therapy
Kinases
Laboratory animals
Lithotripsy
Male
Medicine
Medicine and Health Sciences
Mice
Mice, Inbred C57BL
Muscles
Myocardial ischemia
Myocardium
Neovascularization, Physiologic - radiation effects
Perfusion
Peripheral Vascular Diseases - metabolism
Peripheral Vascular Diseases - therapy
Phosphorylation
Protein Kinases - metabolism
Protein-tyrosine kinase receptors
Quality of life
Receptors
Rodents
Shock
Shock waves
Signaling
Surgery
Therapy
Tyrosine
Ultrasonic Therapy - methods
Vascular endothelial growth factor
Vascular Endothelial Growth Factor Receptor-2 - metabolism
Vascular endothelial growth factor receptors
Ventricle
title Low energy shock wave therapy induces angiogenesis in acute hind-limb ischemia via VEGF receptor 2 phosphorylation
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