title: Ozonetherapy protects from in-stent coronary neointimal proliferation. Role of redoxins.
abstract: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Institute of Cardiological Research, University of Buenos Aires, National Research Council Argentina, ININCA-UBA-CONICET, Argentina.
authors.forename: A
authors.initials: A
authors.lastname: Barone
authors.affiliation: Institute of Cardiological Research, University of Buenos Aires, National Research Council Argentina, ININCA-UBA-CONICET, Argentina.. Electronic address: mol@fmed.uba.ar.
authors.forename: M
authors.initials: M
authors.lastname: Otero-Losada
authors.affiliation: Institute of Cardiological Research, University of Buenos Aires, National Research Council Argentina, ININCA-UBA-CONICET, Argentina.
authors.forename: A M
authors.initials: AM
authors.lastname: Grangeat
authors.affiliation: Institute of Cardiological Research, University of Buenos Aires, National Research Council Argentina, ININCA-UBA-CONICET, Argentina.
authors.forename: G
authors.initials: G
authors.lastname: Cao
authors.affiliation: Institute of Cardiological Research, University of Buenos Aires, National Research Council Argentina, ININCA-UBA-CONICET, Argentina.
authors.forename: F
authors.initials: F
authors.lastname: Azzato
authors.affiliation: Otamendi Hospital, Post Graduate School of Medicine, Cardiac Unit, Buenos Aires, Argentina.
authors.forename: A
authors.initials: A
authors.lastname: Rodríguez
authors.affiliation: Institute of Cardiological Research, University of Buenos Aires, National Research Council Argentina, ININCA-UBA-CONICET, Argentina.
authors.forename: J
authors.initials: J
authors.lastname: Milei
mesh_terms: D000818:Animals; D023903:Coronary Restenosis / Q000097:blood / Q000209:etiology / Q000517:prevention & control; D008297:Male; D058426:Neointima / Q000097:blood* / Q000209:etiology / Q000517:prevention & control*; D010126:Ozone / Q000008:administration & dosage*; D011446:Prospective Studies; D011897:Random Allocation; D016037:Single-Blind Method; D015607:Stents / Q000009:adverse effects*; D013552:Swine; D013879:Thioredoxins / Q000097:blood*
chemical_list: D013879:Thioredoxins; D010126:Ozone
keywords: Coronary angioplasty; Endothelization; Neointimal hyperplasia; Ozonetherapy; Restenosis; Thioredoxin-1