Effect of Matrix Metalloproteinase-9 on Intimal Hyperplasia of Vein Graft

Objective: This study investigated the role of matrix metalloproteinse-9 ( MMP-9 ) in rat model of auto vein graft. Methods: A rat vein graft model was constructed by interposing a jugular vein into the abdominal aorta with end-to-end anastomoses. At the 3rd,7th,and 14th day after the operation, segments of interplanted vein were obtained from Wister rats. Serial sections of vein samples were examined by using Verhoeff elastin staining and MMP-9 immumohisto-chemistry staining. Measurements of neointimal thickness were made using a computerized image analysis system. The quantification of the MMP-9 was tested by substrate gel enzymography. Results: The expression of MMP-9 tented to increase after vein graft. The expression of MMP-9 expression began at the 3rd day, before the formation of intimal hyperpla-sia. Peak expression of MMP-9 occurred by 7 days and remained high, parallelling the development of intimal hyperplasia. The role of MMP-9 in intimal hyperplasis was further investigated by using doxycycline. The intima thickness of rats which received doxycycline was significantly lower than that of rats received nothing ( P 0. 01). We also found that dose-dependent relationship existed between the two groups which received different dosage( P 0. 01). Conclusion: MMP-9 played an important role in imtimal hyperplasia. Doxycycline can significantly reduce neointimal thickening in our model.