Transforming growth factor-beta1 expression and the role of angiotensin-converting enzyme inhibitor on perianastomotic intimal hyperplasia in polytetrafluoroethylene graft implanted in rabbit carotid artery.
The purpose of this study was to evaluate the relationship between intimal hyperplasia and transforming growth factor-beta1 (TGF-beta1) mRNA expression in synthetic arterial grafts and also to clarify the effect of angiotensin-converting enzyme inhibitor (ACEI) on perianastomotic intimal hyperplasia and TGF-beta1 mRNA expression. Thirty New Zealand White rabbits were randomly divided into two groups (15 each); one group was administered Captopril 10 mg/kg/day per os as an ACE inhibitor, and the other group received on saline as a vehicle from 7 days prior to operation until the graft was harvest (1, 8, or 14 weeks). A 10-mm segment of an expanded polytetrafluoroethylene graft (3 mm in diameter) was implanted in the right common carotid artery of the rabbits; 15 rabbits had by-pass grafting alone (Graft Alone group) and the other 15 rabbits had by-pass graft along with the ACEI (Graft plus ACEI group). The artery grafts were harvested. The intima to media height ratio (IMHR) and the TGF-beta1 mRNA expression level in perianastomotic graft tissue by reverse transcription-polymerase chain reaction (RT-PCR). The IMHRs gradually increased from 1 to 14 weeks in both groups (vs. 1 wk in each group, p<0.05). The IMHRs of the Graft plus ACEI group were comparable to those of Graft Alone group at 1 week, but significantly lower at 8 and 14 weeks (vs. Graft Alone group, p<0.05). The TGF-beta1 mRNA expression levels of the Graft plus ACEI group were clearly lower than those of the Graft Alone group at 1 and 8 weeks (vs. Graft Alone group, p<0.05), but similar at 14 weeks. TGF-beta1 in the synthetic artery graft of the Graft Alone group was up-regulated as early as 1 week after the operation, when no definitive development of a quantifiable neointima was observed. The TGF-beta1 mRNA expression of the Graft Alone group was highest at 8 weeks and lowest at 14 weeks (vs. 1 week, *p<0.05), but such time-dependent changes were not observed in the Graft plus ACEI group. The results indicated that ACEI reduced intimal hyperplasia in the grafts of the Graft plus ACEI group and also suppressed TGF-beta1 mRNA expression in perianastomotic intimal hyperplasia tissues to the normal artery level. Perianastomotic intimal hyperplasia in synthetic arterial graft is considered to be related to TGF-beta1, the expression of which is locally mediated by angiotensin II and, therefore, suppressed by ACEI.
Um
Jun Won
JW
Department of Surgery, Korea University College of Medicine, Seoul 136-705, Korea. junwonum@korea.ac.kr
Kim
Jong Man
JM
Min
Byung Wook
BW
Kim
Young Sik
YS
Son
Gil Soo
GS
Lee
Jae Bok
JB
Jung
Suk In
SI
Kim
Seung Joo
SJ
Choi
Sang Yong
SY
Koo
Bum Hwan
BH
Ishibashi
Nobuya
N
Shirouzu
Kazuo
K
Whang
Chung Wung
CW
D000714:Anastomosis, Surgical; D000804:Angiotensin II / Q000502:physiology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D019917:Blood Vessel Prosthesis Implantation; D002216:Captopril / Q000494:pharmacology; D017536:Carotid Artery, Common / Q000601:surgery*; D006965:Hyperplasia; D011138:Polytetrafluoroethylene; D012333:RNA, Messenger / Q000032:analysis*; D011817:Rabbits; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000502:physiology; D053773:Transforming Growth Factor beta1; D017539:Tunica Intima / Q000473:pathology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D000804:Angiotensin II; D011138:Polytetrafluoroethylene; D002216:Captopril