Drew A F, Davenport P, Apostolopoulos J, Tipping P G
Centre for Inflammatory Diseases, Monash University Department of Medicine, Monash Medical Centre, Victoria, Australia.
Lab Invest. 1997 Oct;77(4):291-8.
Tissue factor pathway inhibitor (TFPI) is a potent inhibitor of tissue factor (TF) -initiated coagulation and may play a role in regulating coagulation in atherosclerotic plaques. The expression of TFPI protein and mRNA was examined by immunohistology and in situ hybridization in normal human and rabbit arteries, in human carotid arteries with advanced atherosclerosis, and in atherosclerotic aortas from cholesterol-fed rabbits. In normal human and rabbit arteries, TFPI protein and mRNA were detected in the adventitial layer but were undetectable in the luminal endothelium. In the medial smooth muscle layer of rabbits, weak expression of TFPI mRNA, but not protein, was detected; in that of humans, neither TFPI mRNA nor protein was detectable. In atherosclerotic arteries, TFPI protein and mRNA were detected in three of six internal carotid plaques from patients undergoing endarterectomy, and mRNA alone was detected in one further specimen. TFPI protein was found in areas of the plaque where TF was abundant and colocalized with macrophages, suggesting that these cells are responsible for TFPI synthesis. TFPI protein and mRNA were also detected in fatty-streak lesions in 18 of 19 rabbits fed a high-cholesterol diet for periods between 4 and 16 weeks. In these macrophage-rich lesions, expression of TFPI protein and mRNA was most intense at the base of the plaques. These studies suggest that TFPI is expressed in the adventitial layer of large arteries and that in atherosclerotic vessels, TFPI is expressed by macrophages in focal areas throughout the plaque. Local production of TFPI may regulate procoagulant activity and thrombotic events within atherosclerotic plaques.
组织因子途径抑制物（TFPI）是组织因子（TF）启动的凝血过程的强效抑制剂，可能在调节动脉粥样硬化斑块中的凝血作用中发挥作用。通过免疫组织化学和原位杂交技术，检测了正常人和兔动脉、晚期动脉粥样硬化的人颈动脉以及高胆固醇喂养兔的动脉粥样硬化主动脉中TFPI蛋白和mRNA的表达。在正常人和兔动脉中，TFPI蛋白和mRNA在外膜层被检测到，但在内皮腔中未检测到。在兔的中膜平滑肌层中，检测到TFPI mRNA的弱表达，但未检测到蛋白；在人的中膜平滑肌层中，TFPI mRNA和蛋白均未检测到。在动脉粥样硬化动脉中，在接受内膜切除术患者的六个颈内动脉斑块中的三个中检测到TFPI蛋白和mRNA，在另一个标本中仅检测到mRNA。在斑块中TF丰富且与巨噬细胞共定位的区域发现了TFPI蛋白，表明这些细胞负责TFPI的合成。在19只高胆固醇饮食喂养4至16周的兔子的18只中，在脂肪条纹病变中也检测到了TFPI蛋白和mRNA。在这些富含巨噬细胞的病变中，TFPI蛋白和mRNA的表达在斑块底部最为强烈。这些研究表明，TFPI在大动脉的外膜层表达，并且在动脉粥样硬化血管中，TFPI在整个斑块的局部区域由巨噬细胞表达。TFPI的局部产生可能调节动脉粥样硬化斑块内的促凝血活性和血栓形成事件。
