Sawa H, Fujii S, Sobel B E
Cardiovascular Division, Washington University School of Medicine, St. Louis, MO 63110.
Arterioscler Thromb. 1992 Dec;12(12):1507-15. doi: 10.1161/01.atv.12.12.1507.
Type-1 plasminogen activator inhibitor (PAI-1), the primary physiological inhibitor of endogenous plasminogen activators, modulates fibrinolysis, cell migration, and tissue repair. To determine whether genetic expression of PAI-1 is augmented in the walls of vessels exposed to thrombi but not to a direct physical insult such as electrical injury, we induced arterial thrombosis in rabbit carotid arteries with intraluminal surgical silk sutures and performed in situ hybridization for PAI-1 messenger RNA (mRNA) and immunohistochemistry for PAI-1 antigen at selected intervals. PAI-1 activity in plasma remained virtually constant. In contrast, PAI-1 mRNA increased in endothelial cells juxtaposed to thrombi, in smooth muscle cells adjacent to the neointima, and in macrophages surrounding the suture material. PAI-1 protein was detected in regions in which PAI-1 mRNA was expressed. The increased expression of PAI-1 mRNA colocalized with PAI-1 protein in the endothelium juxtaposed to thrombi may potentiate thrombosis by shifting the local balance between fibrinolysis and thrombosis toward thrombosis. Furthermore, it may alter vascular remodeling and predispose to stenosis after interventions such as angioplasty, in which local thrombosis cannot be avoided.
1型纤溶酶原激活物抑制剂（PAI - 1）是内源性纤溶酶原激活物的主要生理抑制剂，可调节纤维蛋白溶解、细胞迁移和组织修复。为了确定PAI - 1的基因表达在暴露于血栓的血管壁中是否增加，而在诸如电损伤等直接物理损伤的血管壁中不增加，我们用腔内手术丝线在兔颈动脉中诱导动脉血栓形成，并在选定的时间间隔对PAI - 1信使核糖核酸（mRNA）进行原位杂交以及对PAI - 1抗原进行免疫组织化学检测。血浆中的PAI - 1活性几乎保持恒定。相比之下，与血栓相邻的内皮细胞、与新生内膜相邻的平滑肌细胞以及围绕缝合材料的巨噬细胞中的PAI - 1 mRNA增加。在表达PAI - 1 mRNA的区域检测到PAI - 1蛋白。与血栓相邻的内皮细胞中PAI - 1 mRNA表达增加且与PAI - 1蛋白共定位，可能通过将纤维蛋白溶解和血栓形成之间的局部平衡向血栓形成方向转移而增强血栓形成。此外，它可能改变血管重塑，并在诸如血管成形术等无法避免局部血栓形成的干预后易导致狭窄。
