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Training a Sophisticated Microsurgical Technique: Interposition of External Jugular Vein Graft in the Common Carotid Artery in Rats
Published on: November 11, 2012
Rapamycin treatment is associated with an increased apoptosis rate in experimental vein grafts
Thomas Schachner1, Alexander Oberhuber, Yping Zou
1Department of Cardiac Surgery, Medical University Innsbruck, Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria. thomas.schachner@uibk.ac.at
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.
Conclusion:
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.
Insights
Rapamycin treatment increased apoptosis in vein grafts, showing a trend toward reducing neointimal hyperplasia. This suggests apoptosis plays a beneficial role in treating vein graft disease.
Area of Science:
- Vascular Biology
- Immunosuppression
- Cellular Biology
Background:
- Rapamycin is an immunosuppressive drug with antiproliferative effects.
- It is known to reduce restenosis and vein graft neointimal hyperplasia.
- Apoptosis, or programmed cell death, counterbalances cellular proliferation.
Purpose of the Study:
- To investigate the role of apoptosis in rapamycin-treated vein grafts.
- To analyze the effect of rapamycin on neointimal hyperplasia and apoptosis in a mouse model.
Main Methods:
- Interposition of inferior vena cava into the common carotid artery in C57BL6J mice.
- Local application of 200 µg rapamycin in pluronic gel to treatment group; control group received no treatment.
- Morphometric and immunohistochemical (TUNEL) analysis of vein grafts at 4 weeks postoperatively.
Main Results:
- Rapamycin treatment significantly increased apoptosis in the adventitia of vein grafts (P=0.032).
- Neointimal thickness was reduced in rapamycin-treated grafts (17 µm) compared to controls (50 µm).
- No significant difference in apoptosis rate was observed within the neointima between groups.
Conclusions:
- Rapamycin treatment increases apoptosis in the vascular wall of experimental vein grafts.
- Apoptosis may be a beneficial mechanism for reducing neointimal hyperplasia in vein graft disease.
- These findings suggest rapamycin's potential in managing vein graft complications.
