Rapamycin treatment is associated with an increased apoptosis rate in experimental vein grafts.
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.
Schachner
Thomas
T
Department of Cardiac Surgery, Medical University Innsbruck, Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria. thomas.schachner@uibk.ac.at
Oberhuber
Alexander
A
Zou
Yping
Y
Tzankov
Alexandar
A
Ott
Harald
H
Laufer
Günther
G
Bonatti
Johannes
J
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
D007166:Immunosuppressive Agents; D020123:Sirolimus