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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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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. |
format | Online Article Text |
id | pubmed-4122398 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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