Relationship of TGF-beta1 mRNA Expression and Captopril after PTFE Graft in Rabbit Carotid Artery

ABSTRACT

PURPOSE: Intimal hyperplasia (IH) due to vascular smooth muscle cell proliferation is a leading cause of late vascular graft failure. Transforming growth factor-beta1 (TGF-beta1), known to influence smooth muscle cell growth in vascular wall has been subjected for experimental research as a cause of IH. It has been also showed that IH can be mediated by local renin-angiotensin system in vascular intimal injury. Under the assumption that TGF-beta1 and local angiotensin II (ANG II) have a major role as a cause of IH, we carried out this study to see if there are any relationship between intimal hyperplasia and TGF-beta1 mRNA expression, and effect of angiotensin-converting enzyme inhibitor (ACEI) on IH. METHODS: 14 New Zealand White rabbits were subjected for this experiment. The right carotid arteries of 14 rabbits had been bypass grafting with polytetrafluoroethylene. 14 rabbits were allocated into two groups 7 rabbits had bypass grafting only (graft only) and the other 7 rabbits had bypass grafting with ACEI (graft with ACEI). The rabbits, graft with ACEI were on Captopril (10 mg/kg/day PO) from day of operation to 8 weeks when to harvest. There were patent 9 carotid bypass grafts at harvest, and the studies were performed in patent grafts. Intimal hyperplasia was defined by the intima to media height ratio (IMHR). The mRNA expression of TGF-beta1 was determined by semiquantitative RT-PCR. RESULTS: IMHR of graft with ACEI was lower than that of graft (p<0.05). The mRNA expression of TGF-beta1 in graft with ACEI was lower than that in graft only (p<0.05). In summary, there was evidence that TGF-beta1 is closely related with intimal hyperplasia and there is also relationship between ANG II and TGF-beta1. CONCLUSION: ANG II and TGF-beta1 may mediate intimal hyperplasia of vascular graft, and ACE inhibitor may be a armamentarium for inhibition of intimal hyperplasia in vascular graft procedures.