Gene Expression of Transforming Growth Factor-β1, Matrix Metalloprotein-Ase-1, and Matrix Metalloproteinase Tissue Inhibitor-1 in Autogenous Vein Grafts in Rats

Aim To investigate the dynamic expression of transforming growth factor-β1(TGF-β1), matrix metalloproteinase-1(MMP-1), and matrix metalloprotinase tissue inhibitor-1 (TIMP-1), and their relations with intimal hyperplasia in autogenous vein grafts in rats. Methods Animal models were constructed. The vein grafts were collected on day 3, day 7, day 14, and day 28 after operations. HE and Verhoffe staining and computer image analysis system were used to explore the thickness changes of intima and wall at different time points. Western blot and reverse transcription polymerase chain reaction(RT-PCR) were used to detect the protein and mRNA level of TGF-β1, MMP-1, and TIMP-1 in vein grafts and controls. Results Histomorphological analysis showed that the intimal thickness increased remarkably on day 7 after operation compared with control(P0.05), and reached a peak on day 14. Western blot revealed that protein level of TGF-β1 increased on day 3, peaked on day 7 and returned to the baseline on day 28. MMP-1 protein was not significantly different with control on day 3 and 7 respectively, but decreased significantly on day 14 and 28. TIMP-1 protein increased significantly on day 14 and 28. Their mRNA level had similar tendency with the results of Western blot. Conclusions TGF-β1 decreased MMP-1 activity by increasing TIMP-1 expression, and facilitate the excessive accumulation of ECM so as to cause intimal hyperplasia and stenosis.