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

Um, Jun Won; Kim, Young Sik; Jung, Suk In; Choi, Sang Yong; Whang, Cheung Wung

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.