Experimental research on the prevention of autologous vein graft restenosis by fibrin glue combined with tissue inhibitor of metalloproteinase-1

Objective To investigate the mechanism of attenuation of restenosis by applying fibrin glue combined with tissue inhibitor of metalloproteinase-1 (TIMP-1) locally on vein graft.Methods Twenty-four New Zealand white rabbits were randomly divided into 3 groups with 8 rabbits in each group:non-support group (NS group),fibrin glue group (FS group) and fibrin glue + TIMP-1 group (TS/FS group).All animals underwent unilateral jugutar vein into common carotid artery interposition grafting.After operation,vein grafts were harvested at 28th day for histopathologic measurement of intimal thickness,media thickness and intimal areas,media areas,reverse transcription-polymerase chain reaction (RTPCR) and Western blotting analyses of TIMP-1 gene expression.Results At 28th day after the operation,the mean intimal thickness and intimal areas of the TS/FS group were (37.98 ±4.19) μm and (0.557 ±0.049) mm2 respectively,which were reduced obviously as compared with NS group and FS group (P ＜0.05).The mean media thickness and media areas in the TS/FS group were (28.45 ± 3.01 ) μm and (0.458 ±0.053) mm2 respectively,which were decreased statistically as compared with NS group and FS group (P ＜ 0.05).RT-PCR and Western blotting analysis revealed that the gene expression of TIMP-1 was increased in TS/FS group as eompared with NS group and FS group (P ＜ 0.05).Conclusion The expression of TIMP-1 in vein grafts can be up-regulated by adventitial delivery of TIMP-1.The fibrin glue combined with TIMP-1 has synergistic effect on reducing neointimal and media thickness of vein grafts. Key words: Vein graft; Restenosis; Fibrin glue; Tissue inhibitor of metalloproteinase-1