Augmented arterial wall expression of type-1 plasminogen activator inhibitor induced by thrombosis.
Augmented arterial wall expression of type-1 plasminogen activator inhibitor induced by thrombosis.
复制标题
血栓形成诱导的 1 型纤溶酶原激活剂抑制剂的动脉壁表达增强。
DOI：
10.1161/01.atv.12.12.1507
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
Sobel,BE
中科院分区：
文献类型：
--
作者：
Sawa,H;Fujii,S;Sobel,BE
1 型纤溶酶原激活剂抑制剂 (PAI-1) 是内源性纤溶酶原激活剂的主要生理抑制剂，调节纤溶、细胞迁移和组织修复。为了确定暴露于血栓但未暴露于直接物理损伤（例如电损伤）的血管壁中 PAI-1 的基因表达是否增强，我们用腔内手术丝线缝合兔颈动脉诱导动脉血栓形成，并在选定的时间间隔进行 PAI-1 信使 RNA (mRNA) 的原位杂交和 PAI-1 抗原的免疫组织化学分析。血浆中的 PAI-1 活性几乎保持恒定。相反，PAI-1 mRNA 在与血栓相邻的内皮细胞、邻近新内膜的平滑肌细胞以及缝合材料周围的巨噬细胞中增加。在 PAI-1 mRNA 表达的区域检测到 PAI-1 蛋白。与血栓相邻的内皮细胞中 PAI-1 mRNA 与 PAI-1 蛋白共定位的表达增加，可能通过将纤溶和血栓形成之间的局部平衡转向血栓形成来增强血栓形成。此外，它可能会改变血管重塑，并在血管成形术等干预措施后容易出现狭窄，而局部血栓形成是不可避免的。
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.