Department of Pharmacology, Osaka Medical College, Takatsuki City, Osaka, Japan.
J Pharmacol Sci. 2012;119(2):139-49. doi: 10.1254/jphs.11242fp. Epub 2012 May 22.
The neointima formation inside of polytetrafluoroethylene (PTFE) grafts may be associated with the migration of outside fibroblasts to the luminal surfaces. This study aimed to verify whether blockade of fibroblast migration can prevent neointima formation by testing two types of prosthetic vessels, the porous PTFE graft and the impermeable Grasil graft, respectively. After implantation of the PTFE graft in dogs, a time-dependent migration of outside fibroblasts to the luminal side occurred. Compared with the PTFE grafts, the total neointima formation in the Grasil grafts was significantly less. Although the neointima formation at the arterial or venous anastomotic regions did not significantly differ between the two grafts, the neointima at the middle region of the PTFE grafts was significantly evident than the Grasil grafts. The components of the renin–angiotensin system (RAS), such as angiotensin II and its receptor AT1, as well as the forming enzymes of the RAS (angiotensin-converting enzyme and chymase), were all detectable in the grafts' surrounding tissues. Neointima formation at the middle region of the prosthetic vessels could be suppressed almost completely by the blockade of outside fibroblast migration, indicating that outside fibroblasts play a key role in the formation of neointima in this region.
聚四氟乙烯(PTFE)移植物内的新内膜形成可能与外部成纤维细胞向管腔表面迁移有关。本研究旨在通过测试两种类型的人工血管,即多孔 PTFE 移植物和不可渗透的 Grasill 移植物,分别验证阻断成纤维细胞迁移是否可以防止新内膜形成。在犬中植入 PTFE 移植物后,外部成纤维细胞会随时间向管腔侧迁移。与 PTFE 移植物相比,Grasill 移植物中的总新内膜形成明显较少。尽管两种移植物在动脉或静脉吻合区域的新内膜形成没有显著差异,但 PTFE 移植物中间区域的新内膜明显比 Grasill 移植物明显。血管紧张素转化酶和糜酶等肾素-血管紧张素系统(RAS)的形成酶,以及 RAS 的组成成分(血管紧张素 II 和其受体 AT1)在移植物周围组织中均可检测到。通过阻断外部成纤维细胞迁移,可几乎完全抑制移植物中间区域的新内膜形成,表明外部成纤维细胞在该区域新内膜形成中起关键作用。