Extracorporeal shock wave therapy induces therapeutic lymphangiogenesis in a rat model of secondary lymphoedema

Eur J Vasc Endovasc Surg. 2011 Aug;42(2):254-60. doi: 10.1016/j.ejvs.2011.02.029. Epub 2011 Mar 31.

Abstract

Objective: Lymphoedema is a common complication after cancer treatment. We have reported that low-energy extracorporeal shock wave (SW) therapy up-regulates vascular endothelial growth factor (VEGF) in ischaemic myocardium. As VEGF plays an important role in lymphangiogenesis, we investigated whether our low-energy SW therapy enhances lymphangiogenesis in rats.

Methods: We created a tail model of lymphoedema in rats. The tail was treated with or without low-energy SW therapy (0.25 mJ mm(-2), 500 impulses) four times (days 3, 5, 7, and 9). The tail volume and the fluorescence intensity of indocyanine green (ICG) were measured. The expression of VEGF-C and basic fibroblast growth factor (bFGF) were evaluated by RT-PCR, and the lymphatic vessel density was assessed histochemically.

Results: The tail volume increased significantly in the control group and was significantly improved in the SW group. The lymphatic system function (evaluated with fluorescence intensity of ICG), the lymphatic vessel density, and the expression of VEGF-C and bFGF were all enhanced by the SW therapy (all P < 0.05).

Conclusions: The low-energy SW therapy induces therapeutic lymphangiogenesis by up-regulating VEGF-C and bFGF, and improves lymphoedema in a rat-tail model, suggesting that low-energy SW therapy could be a non-invasive and effective strategy for lymphoedema in humans.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Fibroblast Growth Factor 2 / genetics
  • Fibroblast Growth Factor 2 / metabolism
  • Lymphangiogenesis*
  • Lymphatic System / metabolism
  • Lymphatic System / physiopathology*
  • Lymphedema / genetics
  • Lymphedema / metabolism
  • Lymphedema / physiopathology
  • Lymphedema / therapy*
  • Male
  • RNA, Messenger
  • Rats
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Polymerase Chain Reaction
  • Serum Albumin / metabolism
  • Time Factors
  • Ultrasonic Therapy*
  • Up-Regulation
  • Vascular Endothelial Growth Factor C / genetics
  • Vascular Endothelial Growth Factor C / metabolism

Substances

  • RNA, Messenger
  • Serum Albumin
  • Vascular Endothelial Growth Factor C
  • Fibroblast Growth Factor 2