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Low Energy Shock Wave Therapy Induces Angiogenesis in Acute Hind-Limb Ischemia via VEGF Receptor 2 Phosphorylation

OBJECTIVES: 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. METHODS: Hind-l...

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Autores principales: Holfeld, Johannes, Tepeköylü, Can, Blunder, Stefan, Lobenwein, Daniela, Kirchmair, Elke, Dietl, Marion, Kozaryn, Radoslaw, Lener, Daniela, Theurl, Markus, Paulus, Patrick, Kirchmair, Rudolf, Grimm, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4122398/
https://www.ncbi.nlm.nih.gov/pubmed/25093816
http://dx.doi.org/10.1371/journal.pone.0103982
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author Holfeld, Johannes
Tepeköylü, Can
Blunder, Stefan
Lobenwein, Daniela
Kirchmair, Elke
Dietl, Marion
Kozaryn, Radoslaw
Lener, Daniela
Theurl, Markus
Paulus, Patrick
Kirchmair, Rudolf
Grimm, Michael
author_facet Holfeld, Johannes
Tepeköylü, Can
Blunder, Stefan
Lobenwein, Daniela
Kirchmair, Elke
Dietl, Marion
Kozaryn, Radoslaw
Lener, Daniela
Theurl, Markus
Paulus, Patrick
Kirchmair, Rudolf
Grimm, Michael
author_sort Holfeld, Johannes
collection PubMed
description OBJECTIVES: 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. METHODS: 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/mm(2), 5 Hz) and untreated controls (CTR), n = 10 per group. The treatment group received shock wave therapy immediately after surgery. RESULTS: 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. CONCLUSIONS: 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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spelling pubmed-41223982014-08-12 Low Energy Shock Wave Therapy Induces Angiogenesis in Acute Hind-Limb Ischemia via VEGF Receptor 2 Phosphorylation Holfeld, Johannes Tepeköylü, Can Blunder, Stefan Lobenwein, Daniela Kirchmair, Elke Dietl, Marion Kozaryn, Radoslaw Lener, Daniela Theurl, Markus Paulus, Patrick Kirchmair, Rudolf Grimm, Michael PLoS One Research Article OBJECTIVES: 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. METHODS: 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/mm(2), 5 Hz) and untreated controls (CTR), n = 10 per group. The treatment group received shock wave therapy immediately after surgery. RESULTS: 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. CONCLUSIONS: 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. Public Library of Science 2014-08-05 /pmc/articles/PMC4122398/ /pubmed/25093816 http://dx.doi.org/10.1371/journal.pone.0103982 Text en © 2014 Holfeld et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Holfeld, Johannes
Tepeköylü, Can
Blunder, Stefan
Lobenwein, Daniela
Kirchmair, Elke
Dietl, Marion
Kozaryn, Radoslaw
Lener, Daniela
Theurl, Markus
Paulus, Patrick
Kirchmair, Rudolf
Grimm, Michael
Low Energy Shock Wave Therapy Induces Angiogenesis in Acute Hind-Limb Ischemia via VEGF Receptor 2 Phosphorylation
title Low Energy Shock Wave Therapy Induces Angiogenesis in Acute Hind-Limb Ischemia via VEGF Receptor 2 Phosphorylation
title_full Low Energy Shock Wave Therapy Induces Angiogenesis in Acute Hind-Limb Ischemia via VEGF Receptor 2 Phosphorylation
title_fullStr Low Energy Shock Wave Therapy Induces Angiogenesis in Acute Hind-Limb Ischemia via VEGF Receptor 2 Phosphorylation
title_full_unstemmed Low Energy Shock Wave Therapy Induces Angiogenesis in Acute Hind-Limb Ischemia via VEGF Receptor 2 Phosphorylation
title_short Low Energy Shock Wave Therapy Induces Angiogenesis in Acute Hind-Limb Ischemia via VEGF Receptor 2 Phosphorylation
title_sort low energy shock wave therapy induces angiogenesis in acute hind-limb ischemia via vegf receptor 2 phosphorylation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4122398/
https://www.ncbi.nlm.nih.gov/pubmed/25093816
http://dx.doi.org/10.1371/journal.pone.0103982
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