title: Rapamycin treatment is associated with an increased apoptosis rate in experimental vein grafts.
abstract: OBJECTIVE
  Rapamycin is an immunosuppressive agent with marked antiproliferative properties and is effective in reducing in stent restenosis and vein graft neointimal hyperplasia. Apoptosis is one mechanism counterbalancing cellular proliferation. We therefore investigated the role of apoptosis in rapamycin treated vein grafts in a mouse model.
  
  
  METHODS
  C57BL6J mice underwent interposition of the inferior vena cava from isogenic donor mice into the common carotid artery using a cuff technique. In the treatment group 200 microg of rapamycin were applied locally in pluronic gel. The control group did not receive local treatment. Vein grafts were harvested at 4 weeks postoperatively and underwent morphometric analysis as well as immunohistochemical analysis for apoptosis (TUNEL).
  
  
  RESULTS
  In grafted veins without treatment (controls) neointimal thickness was 50 (12-58) microm at 4 weeks postoperatively. In 200 microg rapamycin treated grafts the neointimal thickness was 17 (5-55) microm. Rapamycin treated vein grafts showed a significantly increased rate of apoptosis in the adventitia as compared with controls (P=0.032). In the neointima the apoptosis rate was lower in both groups with no significant difference between rapamycin treated grafts and controls.
  
  
  CONCLUSIONS
  We conclude that treatment of experimental vein grafts with rapamycin is associated with an increased apoptosis rate in the vascular wall and a trend towards reduction of neointimal hyperplasia. These results suggest that apoptosis may be a beneficial antiproliferative component for the treatment of vein graft disease.
authors.affiliation: Department of Cardiac Surgery, Medical University Innsbruck, Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria. thomas.schachner@uibk.ac.at
authors.forename: Thomas
authors.initials: T
authors.lastname: Schachner
authors.forename: Alexander
authors.initials: A
authors.lastname: Oberhuber
authors.forename: Yping
authors.initials: Y
authors.lastname: Zou
authors.forename: Alexandar
authors.initials: A
authors.lastname: Tzankov
authors.forename: Harald
authors.initials: H
authors.lastname: Ott
authors.forename: Günther
authors.initials: G
authors.lastname: Laufer
authors.forename: Johannes
authors.initials: J
authors.lastname: Bonatti
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D023903:Coronary Restenosis / Q000517:prevention & control*; D006083:Graft Occlusion, Vascular / Q000517:prevention & control*; D006965:Hyperplasia; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D020287:In Situ Nick-End Labeling; D051379:Mice; D008807:Mice, Inbred BALB C; D020123:Sirolimus / Q000627:therapeutic use*; D015607:Stents; D017539:Tunica Intima / Q000473:pathology
chemical_list: D007166:Immunosuppressive Agents; D020123:Sirolimus