Mithramycin inhibits intimal hyperplasia of vein grafts after transplantation of the jugular vein to the abdomainal aorta in rats.
OBJECTIVE: The intimal hyperplasia caused by mig ration and proliferation of the smooth muscle cells play a most important role in the stenosis of the vein grafts. This study is to explore how the C-myc onc ogene and its protein contribute to the intimal hyperplasia after the jugular ve in is transplanted to the abdominal aorta and to assess the effect of Mithramyci n on the intimal hyperplasia. METHODS: In 60 Wistar rats, a 0.8 cm segment of the right j ugular vein graft was interposed at the level of the abdominal aorta. The experi ment group received Mithramycin (150 mug/kg IP) 1 h before and after the operat ion. The control group received normal saline, specimens of vein graft at 2 and 6 h postoperatively were subjected respectively to in situ hybridization. The ve in grafts 4 weeks after operation were perfusion fixed. The specimens were stain ed with hemotoxylin-eosin and the computer morphologic analysis system was used to evaluate the degree of intimal thickening. Immunohistochemistry studies of m uscle-specific &amg;-actin, C-myc protein and 5'-Bromodeoxyuridine were perfor med. RESULTS: The areas of neointimal and the ratios of neointimal t o medial area were significantly smaller and lower in the Mithramycin-treated t han in the control rats (P<0.05). The 5'-Brdu labeli ng rate between the two groups were also different significantly (P<0.05). Muscl-specific alpha-actin showed that the smooth muscle ce lls formed the most area of myointimal hyperplasia. Steady-state C-myc mRNA le vel was incre ased from 2 h to 6 h postoperatively. The positive rate of the placebo-treated group was higher significantly than that of the Mithramycin-treated group (P<0.05). CONCLUSIONS: Mithramycin may effectively inhibits transcription of C-myc in proliferating vascular smooth muscle cells and could be useful in the prevention of restenosis after vascularization. These results support the hy pothesis that systemic administration of Mithramycin might immediately prevent i ntimal proliferation.
Wang
Bin
B
Department of General Surgery, 202nd Hospital of PLA, Shenyang 110003, China.
Wang
Xinwen
X
Duan
Zhiquan
Z