Ozonetherapy protects from in-stent coronary neointimal proliferation. Role of redoxins

Int J Cardiol. 2016 Nov 15:223:258-261. doi: 10.1016/j.ijcard.2016.07.177. Epub 2016 Jul 29.


Background: In-stent restenosis and poor re-endothelization usually follow percutaneous transluminal coronary angioplasty, even using drug-eluting stents, due to inflammation and oxidative stress. Medical ozone has antioxidant and anti-inflammatory properties and has not been evaluated in this context.

Objectives: To evaluate whether ozonotherapy might reduce restenosis following bare metal stents implantation in relation to the redoxin system in pigs.

Methods: Twelve male Landrace pigs (51±9kg) underwent percutaneous transluminal circumflex coronary arteries bare metal stent implantation under heparine infusion and fluoroscopical guidance, using standard techniques. Pigs were randomized to ozonetherapy (n=6) or placebo (n=6) treatment. Before stenting (24h) and twice a week for 30days post-stenting, venous blood was collected, ozonized and reinfused. Same procedure was performed in placebo group except for ozonation. Both groups received antiplatelet treatment. Histopathology and immunohistochemistry studies were performed.

Results: Severe inflammatory reaction and restenosis with increase in the immunohistochemical expression of thioredoxin-1 were observed in placebo group 30days after surgery. Oppositely, ozonetherapy drastically reduced inflammatory reaction and restenosis, and showed no increase in the Trx-1 immunohistochemical expression 30days after surgery. Immunolabeling for Prx-2 was negative in both groups. Ozonated autohemotherapy strikingly reduced restenosis 30days following PTCA with BMS implantation in pigs.

Conclusions: Stimulation of the redoxin system by ozone pretreatment might neutralize oxidative damage from the start and increase antioxidative buffering capacity post-injury, reducing further damage and so the demand for antioxidant enzymes. Our interpretation agrees with the ozone oxidative preconditioning mechanism, extensively investigated.

Keywords: Coronary angioplasty; Endothelization; Neointimal hyperplasia; Ozonetherapy; Restenosis; Thioredoxin-1.

MeSH terms

  • Animals
  • Coronary Restenosis / blood
  • Coronary Restenosis / etiology
  • Coronary Restenosis / prevention & control
  • Male
  • Neointima / blood*
  • Neointima / etiology
  • Neointima / prevention & control*
  • Ozone / administration & dosage*
  • Prospective Studies
  • Random Allocation
  • Single-Blind Method
  • Stents / adverse effects*
  • Swine
  • Thioredoxins / blood*


  • Thioredoxins
  • Ozone