Experimental Study Of Mechanism Of Intinal Hyperplasia Of Vein Graft After CABG And The Effect Of Losartan On Intimal Hyperplasia

OBJECTIVES : Intimal hyperplasia in grafts of coronary artery bypass grafting contributes to graft failure. However, the mechanism of intimal hyperplasia of venous grafts has not been elucidated, therefore, we investigated it to confirm the main factor affecting the intimal hyperplasia after coronary artery bypass grafting (CABG), to study the effects of angiotensin II (ANGII) and transforming growth factor P (TGF 3 ) on intimal hyperplasia and the relationship between ANG II and TGF 3 , and to study the effect of Losartan on intimal hyperplasia and its mechanism.METHODS: New Zealand rabbits were employed to establish the animal model with anastomosis of external)ugular vein to ipsilateral carotid artery by end-to-side fashion. The vessels were sectioned , and immunostained for the expression of the proliferation marker proliferating cell nuclear antigen (PCNA). The number of cells of positive PCNA and proliferative index (PCNA positive nuclei/total nuclei) was calculated. With technique of reverse transcription-polymerase chain reaction (RT-PCR), the changes of mRNA of TGFβ , AT1R, collagen I and collagen III were detected by semiquantitative methods. 4 weeks after operation the vein grafts were sectioned and stained by VG method, and luminal area, intima, and media were measured.RESULTS: 1. 4 weeks after operation, the neointimal lesions in the grafts anastomosed to carotid artery were increased obviously in size compared to the lesions in the grafts anastomosed in situ. Meanwhile in the grafts anastomosed to carotid artery the values of mRNA of TGF β , AT1R, collagen I and collagen III detected by RT-PCR method were higher than the values in the grafts anastomosed in situ (P<0.01) . 2. At different time the values of mRNA of TGF 3 , AT1R, collagen I and collagen III in both groupsthe were measured. At 2nd weeks after operation the values reached peaks and the state were continuous until 4th weeks. Moreover, thevalues in grafts anastomosed to carotid artery were higher compared to the values in the grafts anastomosed in situ(P<0.01). 3. After 4 weeks of treatment with Losartan, the neointimal lesions in treatment group were decreased markedly in size compared to control group (P<0.01) . The number of cells with positive PCNA in treatment group were decreased than that in control group (P<0.01) . The values of mRNA of TGF β , AT1R, collagen I and collagen III in treatment group were reduced (P< 0.01 compared to control group) .CONCLUSIONS: 1. Continuous pressure is the main factor to cause the intimal hyperplasia in vein grafts fater CABG. 2. Under the pressure the ANGII is produced in vein grafts after CABG. Binding the ANG II to AT1R triggers the expression of TGF β which causes the transferation and proliferation of the smooth muscle cells (SMC) and myofibroblasts resulting in the intimal hyerplasia. 3. Blocking the binding ANG II to AT1R by Losartan can diminish the production of TGFβ and inhibit the intimal hyerplasia.