Increased intramural expression of plasminogen activator inhibitor type 1 after balloon injury: a potential progenitor of restenosis.
Increased intramural expression of plasminogen activator inhibitor type 1 after balloon injury: a potential progenitor of restenosis.
复制标题
球囊损伤后 1 型纤溶酶原激活剂抑制剂壁内表达增加：再狭窄的潜在祖细胞。
DOI：
10.1016/0735-1097(94)90182-1
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发表时间：
1994
影响因子：
24
通讯作者：
Fujii,S
中科院分区：
文献类型：
--
作者：
Sawa,H;Lundgren,C;Sobel,BE;Fujii,S
目标。本研究旨在探讨实验性球囊损伤后动脉壁内纤溶酶原激活物抑制物-1(PAI-1)基因表达是否发生改变。已知的PAI-1可以抑制循环中的纤溶，存在于动脉粥样硬化的血管中，可能会影响血管成形术后动脉壁的蛋白分解和新生内膜的形成。采用Northern印迹、原位杂交和免疫组织化学方法对兔颈总动脉球囊损伤后PAI-1基因和蛋白表达进行检测。在未损伤的正常血管中，Northern印迹和原位杂交检测不到PAI-1信使核糖核酸(MRNA)。然而，损伤后3h内，PAI-1mRNA(3.2kb)的表达较对侧对照颈动脉(Northern Blots)增加5.9倍。原位杂交法检测到PAI-1mRNA在伤后早期即可在外膜表达，伤后24小时在中膜表达尤为明显。损伤后1~4周内可持续检测到，且在新生内膜明显增厚时定位于新生内膜、血管平滑肌和内皮细胞。免疫组织化学检测两种细胞均表达PAI-1蛋白。在活体球囊损伤后维持在器官培养中的血管中，PAI-1活性也在条件培养液中持续增加。我们的结果表明，模拟血管成形术的球囊损伤诱导了血管平滑肌和内皮细胞壁内PAI-1的表达。PAI-1表达增加可能导致细胞表面纤溶活性降低，可能引发或加剧壁血栓形成。因此，血栓相关丝裂原的过度刺激可能刺激血管平滑肌细胞的增殖，再加上由于纤溶酶介导的降解减少而导致的细胞外基质堆积增加，可能导致再狭窄。
Objectives. This study was performed to determine whether altered gene expression of plasminogen activator inhibitor type I (PAI-1) occurs within the arterial wall after experimentally induced balloon injury.Background. PAI-1, known to inhibit fibrinolysis in the circulation and to be present within atherosclerotic vessels, may influence proteolysis in the arterial wall and neointimal formation after angioplasty.Methods. In rabbit carotid arteries subjected to balloon injury, both PAI-1 gene and protein expression were assayed sequentially with the use of Northern blotting, in situ hybridization and immunohistochemical studies.Results. In uninjured, normal vessels PAI-1 messenger ribonucleic acid (mRNA) was not detectable by Northern blotting or in situ hybridization. However, injury was followed within 3 h by increases in PAI-1 mRNA (3.2 kb) of 5.9-fold compared with that in contralateral control carotid arteries (Northern blots). PAI-1 mRNA was detectable by in situ hybridization early after injury first in adventitia; after 24 h it was particularly prominent in the media. From 1 to 4 weeks after injury it was consistently detectable and was localized in neointimal vascular smooth muscle and endothelial cells at a time when neointimal thickening was marked. Cells of both types exhibited PAI-1 protein detected immunohistochemically. In vessels maintained in organ culture after balloon injury in vivo, sustained increases in PAI-1 activity appeared in conditioned media as well.Conclusions. Our results indicate that balloon injury simulating angioplasty in patients induces intramural expression of PAI-1 in vascular smooth muscle and endothelial cells. The decreased cell surface fibrinolytic activity likely to result from the increased PAI-1 expression may initiate or exacerbate mural thrombosis. Accordingly, excessive stimulation with clot-associated mitogens may stimulate vascular smooth muscle cell proliferation, which, coupled with increased accumulation of extracellular matrix attributable to decreased plasmin-mediated degradation, may contribute to restenosis.