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PLoS One. 2014 Aug 5;9(8):e103982. doi: 10.1371/journal.pone.0103982. eCollection 2014.

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

Author information

1
University Hospital for Cardiac Surgery, Innsbruck Medical University, Innsbruck, Austria.
2
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.
3
University Hospital for Dermatology and Venerology, Innsbruck Medical University, Innsbruck, Austria.
4
University Hospital for Internal Medicine III, Department of Cardiology and Angiology, Innsbruck Medical University, Innsbruck, Austria.
5
Clinic of Anaesthesiology, Intensive Care Medicine and Pain Therapy, Goethe-University Hospital, Frankfurt am Main, Germany.

Abstract

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.

PMID:
25093816
PMCID:
PMC4122398
DOI:
10.1371/journal.pone.0103982
[Indexed for MEDLINE]
Free PMC Article

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