TY - JOUR A1 - Holfeld, Johannes A1 - Tepeköylü, Can A1 - Blunder, Stefan A1 - Lobenwein, Daniela A1 - Kirchmair, Elke A1 - Dietl, Marion A1 - Kozaryn, Radoslaw A1 - Lener, Daniela A1 - Theurl, Markus A1 - Paulus, Patrick A1 - Kirchmair, Rudolf A1 - Grimm, Michael T1 - Low energy shock wave therapy induces angiogenesis in acute hind-limb ischemia via VEGF receptor 2 phosphorylation T2 - PLoS One N2 - 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/mm2, 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. Y1 - 2014 UR - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/35038 UR - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-350388 SN - 1932-6203 N1 - Copyright: © 2014 Holfeld et al. 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 credited. VL - 9 IS - (8):e103982 PB - PLoS CY - Lawrence, Kan. ER -