Inhibiton Effects Of Rosiglitazone On Intimal Hyperplasia In Autologous Vein Grafts

ObjectiveAutologous vein graft is the routine operation for ischemic diseases in cardiac and vascular surgery. However, the long - term patent rate of grafted vein currently is low. The unfavorable treating effect is mainly due to stenosis and occlusion on account of intimal hyperplasi-a. The pivot pathologic mechanisms of intimal hyperplasia are the migration into intima and proliferation of medial smooth muscle cell (SMC). Peroxisome proliferator - activated receptors (PPARs) are ligands activated nuclear transcription factor. The relationship between PPARr, one of isoforms of PPARs, and cardiovascular diseases was paid more attention recently. We observed the effect of Rosiglitazone, a PPARr highly specific agonist, on SMC of rat grafted vein, consequently study preliminarily the relationship between PPARr and intimal hyperplasia.MethodsRat autologous vein graft model was established and 57 Wistarrats were divided into three groups at random: the experimental group (administered Rosiglitazone 3mg/kg/d and 0. 5% Methylcellulose 3. 8ml/kg/d by gavage from the 7th day before operation to the day for harvesting) , the solvent control group(administered 0.5% Methylcellulose 3. 8ml/kg/d by gavage from the 7th day before operation to the day for harvesting) and the blank control group (the sham operation group). The grafted veins were harvested at the 3rd, 7th and 14th day respectively after the operation, detected and compared in several parts between the different groups or phases as follows: the status and the time course changing of intimal hyperplasia after vein graft which were observed by some morphologic methods ( Haematoxylin - Eosin staining and Verhoeff - Van Gieson staining) ; the expression of matrix metalloproteinase - 9 ( MMP - 9 ) and proliferating cell nuclear antigen (PCNA) by immunohistochemical staining and analyzed by computer digitizing system. Correlation analysis between the immunohistochemical results of MMP - 9 and those of PCNA was proceeded by Spearman method.Results(1) The average thickness of grafted vein; those of the experimental group at the 7th and 14th day were distinctly lesser than those of the blank control group (P <0. 05 at the 7th day, P <0. 01 at the 14th day) and those of the solvent control group ( P < 0. 01)- in the same phase. (2) The percentage of the positive MMP -9 immunohistochemical stained cells: that of the experimental group was distinctly lesser than those of the blank control group and the solvent control group (P < 0. 05 at the 3rd day, P < 0. 01 at the 7th and the 14thday). The difference of positive staining between the different phases in the same group was significant. (3) The percentage of the positive PCNA immunohistochemical stained cells; that of the experimental group was distinctly lesser than those of the two control groups in the same phase (P <0. 05 at the 3rd day, P <0. 01 at the 7th and 14th day). The difference of positive PCNA staining between the different phases in the same group was significant. (4) Spearman correlation coefficients: the blank control group was 0. 843; the solvent control group was 0. 810; the experimental group was 0. 746 and the total was 0. 873. The P value(2 -tailed) of all the group was <0. 001.Conclusions(1) Rosiglitazone can inhibit intimal hyperplasia on autologous vein graft in rat. (2) Rosiglitazone can inhibit the expression of MMP - 9 of SMC, so probably inhibit the degradation of extracellular matrix and the migration of vascular smooth muscle cell; can inhibit the proliferation of vascular smooth muscle cell. ( 3 ) The effects above maybe were achieved by activating PPARr of vascular SMC.