Related Experiment Video
Updated: Jul 11, 2026
Seeding and Implantation of a Biosynthetic Tissue-engineered Tracheal Graft in a Mouse Model
Published on: April 1, 2019
Roles of chymase in stenosis occurring after polytetrafluoroethylene graft implantations
Denan Jin1, Haruhiko Ueda, Shinji Takai
1Department of Pharmacology, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki City, Osaka 569-8686, Japan. pha012@art.osaka-med.ac.jp
Insights
Chymase inhibition reduces neointimal hyperplasia after polytetrafluoroethylene graft implantation. Blocking chymase, which promotes angiotensin II and TGF-beta1, may prevent hemodialysis access dysfunction.
Area of Science:
- Vascular Biology
- Enzymology
- Surgical Research
Background:
- Hemodialysis access dysfunction is often caused by intimal hyperplasia after polytetrafluoroethylene (PTFE) graft implantation.
- Chymase, an enzyme, generates angiotensin II and activates transforming growth factor-beta1, suggesting its potential role in this process.
Purpose of the Study:
- To investigate the role of chymase in neointimal hyperplasia following PTFE graft implantation.
- To evaluate the efficacy of a chymase inhibitor (NK3201) in preventing PTFE graft dysfunction.
Main Methods:
- Bilateral PTFE grafts were implanted in dogs.
- Dogs received a chymase inhibitor (NK3201) orally starting 3 days pre-operation.
- Neointimal formation, cellular components, and expression of chymase, Ang II, TGF-beta1, and their receptors were analyzed.
Main Results:
- Neointimal hyperplasia and stenosis were frequently observed in the venous side of PTFE grafts.
- Chymase-positive mast cells accumulated around grafts, with co-localization of Ang II and TGF-beta1 positive cells.
- Chymase inhibitor treatment significantly reduced chymase, Ang II, and TGF-beta1 expression, inhibiting neointimal formation.
Conclusions:
- Increased chymase activity promotes Ang II and TGF-beta1 generation, playing a key role in PTFE graft neointimal formation.
- Chymase inhibition is a potential therapeutic strategy to prevent PTFE graft dysfunction in clinical settings.
Abstract:
Chymase is an important enzyme for the generation of angiotensin (Ang) II and in the activation of transforming growth factor (TGF)-beta1. Therefore, chymase may be involved in the hemodialysis access dysfunction, which is caused by intimal hyperplasia that occurs after polytetrafluoroethylene (PTFE) graft implantations. Bilateral U-shaped PTFE grafts were placed between the femoral vein and artery in dogs. Chymase inhibitor (NK3201, 1 mg/kg per day, p.o.) treatments were initiated 3 days before the operation. After the implantation, the stenosis by neointima proliferation was most frequently observed in the venous side of the PTFE grafts. In the hyperplastic neointima, myofibroblasts were the main cellular components. On the other hand, fibroblasts only occupied cellular components in a much smaller proportion in the neointima. However, these cells seem to be rich in the properties of proliferation and migration. After PTFE graft implantations, extensive accumulations of chymase-positive mast cells were found mainly in the tissue surrounding the grafts. The Ang II- and TGF-beta-positive cells were found in an adjacent section that was in close proximity to the chymase-positive cells. In contrast, the AT(1) receptors, as well as TGF-beta type II receptors, were expressed either in the neointima or in the outside adventitia of the PTFE grafts. Chymase inhibitor treatment resulted in a reduction of chymase, Ang II and TGF-beta1 expression, leading to a significant inhibition of neointimal formation. These findings indicating that an increase of chymase via promoting Ang II and TGF-beta1 generation plays a pivotal role in the neointimal formation after the implantation of PTFE grafts and also suggesting that chymase inhibition may be a new strategy that can be used to prevent PTFE graft dysfunctions in clinical settings.
