Transforming growth factor- β1 expression and the role of angiotensin-converting enzyme inhibitor on perianastomotic intimal hyperplasia in polytetrafluoroethylene graft implanted in rabbit carotid artery

Jun Won Um, Jong Man Kim, Byung Wook Min, Young Sik Kim, Gil Soo Son, Jae Bok Lee, Suk In Jung, Seung Joo Kim, Sang Yong Choi, Bum Hwan Koo, Nobuya Ishibashi, Kazuo Shirouzu, Chung Wung Whang

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The purpose of this study was to evaluate the relationship between intimal hyperplasia and transforming growth factor- β1 (TGF- β1) mRNA expression in synthetic arterial grafts and also to clarify the effect of angiotensin-converting enzyme inhibitor (ACEI) on perianastomotic intimal hyperplasia and TGF- β1 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- β1 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- β1 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- β1 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- β1 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- β1 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- β1, the expression of which is locally mediated by angiotensin II and, therefore, suppressed by ACEI.

Original languageEnglish
Pages (from-to)235-243
Number of pages9
JournalKurume Medical Journal
Volume51
Issue number3-4
Publication statusPublished - 2004 Dec 1

Fingerprint

Tunica Intima
Polytetrafluoroethylene
Transforming Growth Factors
Carotid Arteries
Angiotensin-Converting Enzyme Inhibitors
Hyperplasia
Rabbits
Transplants
Messenger RNA
Arteries

Keywords

  • Angiotensin-converting enzyme inhibitors
  • Carotid arteries
  • Polytetrafluoroethylene
  • Rabbits
  • Transforming growth factor beta
  • Tunica intima

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Transforming growth factor- β1 expression and the role of angiotensin-converting enzyme inhibitor on perianastomotic intimal hyperplasia in polytetrafluoroethylene graft implanted in rabbit carotid artery. / Um, Jun Won; Kim, Jong Man; Min, Byung Wook; Kim, Young Sik; Son, Gil Soo; Lee, Jae Bok; Jung, Suk In; Kim, Seung Joo; Choi, Sang Yong; Koo, Bum Hwan; Ishibashi, Nobuya; Shirouzu, Kazuo; Whang, Chung Wung.

In: Kurume Medical Journal, Vol. 51, No. 3-4, 01.12.2004, p. 235-243.

Research output: Contribution to journalArticle

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AU - Um, Jun Won

AU - Kim, Jong Man

AU - Min, Byung Wook

AU - Kim, Young Sik

AU - Son, Gil Soo

AU - Lee, Jae Bok

AU - Jung, Suk In

AU - Kim, Seung Joo

AU - Choi, Sang Yong

AU - Koo, Bum Hwan

AU - Ishibashi, Nobuya

AU - Shirouzu, Kazuo

AU - Whang, Chung Wung

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N2 - The purpose of this study was to evaluate the relationship between intimal hyperplasia and transforming growth factor- β1 (TGF- β1) mRNA expression in synthetic arterial grafts and also to clarify the effect of angiotensin-converting enzyme inhibitor (ACEI) on perianastomotic intimal hyperplasia and TGF- β1 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- β1 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- β1 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- β1 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- β1 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- β1 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- β1, the expression of which is locally mediated by angiotensin II and, therefore, suppressed by ACEI.

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KW - Carotid arteries

KW - Polytetrafluoroethylene

KW - Rabbits

KW - Transforming growth factor beta

KW - Tunica intima

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