title: Low energy shock wave therapy induces angiogenesis in acute hind-limb ischemia via VEGF receptor 2 phosphorylation.
abstract: OBJECTIVE
  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.
authors.affiliation: University Hospital for Cardiac Surgery, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Johannes
authors.initials: J
authors.lastname: Holfeld
authors.affiliation: University Hospital for Cardiac Surgery, Innsbruck Medical University, Innsbruck, Austria; Division of Clinical and Functional Anatomy, Department of Anatomy, Histology and Embryology, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Can
authors.initials: C
authors.lastname: Tepeköylü
authors.affiliation: University Hospital for Dermatology and Venerology, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Blunder
authors.affiliation: University Hospital for Cardiac Surgery, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Daniela
authors.initials: D
authors.lastname: Lobenwein
authors.affiliation: University Hospital for Cardiac Surgery, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Elke
authors.initials: E
authors.lastname: Kirchmair
authors.affiliation: University Hospital for Cardiac Surgery, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Marion
authors.initials: M
authors.lastname: Dietl
authors.affiliation: University Hospital for Cardiac Surgery, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Radoslaw
authors.initials: R
authors.lastname: Kozaryn
authors.affiliation: University Hospital for Internal Medicine III, Department of Cardiology and Angiology, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Daniela
authors.initials: D
authors.lastname: Lener
authors.affiliation: University Hospital for Internal Medicine III, Department of Cardiology and Angiology, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Markus
authors.initials: M
authors.lastname: Theurl
authors.affiliation: Clinic of Anaesthesiology, Intensive Care Medicine and Pain Therapy, Goethe-University Hospital, Frankfurt am Main, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Paulus
authors.affiliation: University Hospital for Internal Medicine III, Department of Cardiology and Angiology, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Kirchmair
authors.affiliation: University Hospital for Cardiac Surgery, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Grimm
mesh_terms: D000208:Acute Disease; D000818:Animals; D019220:High-Energy Shock Waves / Q000627:therapeutic use*; D006614:Hindlimb / Q000098:blood supply* / Q000528:radiation effects; D007511:Ischemia / Q000378:metabolism / Q000628:therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000528:radiation effects*; D016491:Peripheral Vascular Diseases / Q000378:metabolism / Q000628:therapy; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D014464:Ultrasonic Therapy / Q000379:methods*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
chemical_list: D011494:Protein Kinases; C000592875:Kdr protein, mouse; D040301:Vascular Endothelial Growth Factor Receptor-2
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