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DOI: 10.1055/s-2005-922345
Perivascular treatment with azathioprine reduces neointimal hyperplasia in experimental vein grafts
Background: Azathioprine is an immunosuppressive and anti-inflammatory drug and it has been shown to induce apoptosis in human T lymphocytes. We investigated whether local treatment with azathioprine can inhibit neointimal hyperplasia in experimental vein grafts.
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 azathioprine was applied perivascularly. The control group did not receive local treatment. Vein grafts were harvested at 1 and 2 weeks postoperatively and underwent morphometric analysis as well as immunohistochemical analysis for apoptosis (TUNEL).
Results: In grafted veins without treatment (controls) neointimal thickness was 10 (6–29)µm, and 12 (8–40)µm at 1, and 2 weeks postoperatively. In azathioprine treated grafts the neointimal thickness was 2 (1–5)µm, and 4 (3–11)µm. This reduction of neointimal thickness was significant at 1 week (p=0.001) and 2 weeks (p=0.016) postoperatively. Azathioprine treated vein grafts showed an increased rate of apoptosis in the vascular wall as compared with controls (593 (26–783) vs. 45 (0–106) apoptotic cells/mm2 at 1 week, p=0.063, and 656 (327–1270) vs. 19 (0–79) apoptotic cells/mm2 at 2 weeks, p=0.016).
Conclusions: We conclude that treatment of experimental vein grafts with azathioprine is associated with a reduction of neointimal hyperplasia and an increased apoptosis rate in the vascular wall. These results suggest that azathioprine may be useful for the prevention of vein graft disease.