ANGIOTENSIN-II REGULATES THE EXPRESSION OF PLASMINOGEN-ACTIVATOR INHIBITOR-1 IN CULTURED ENDOTHELIAL-CELLS - A POTENTIAL LINK BETWEEN THE RENIN-ANGIOTENSIN SYSTEM AND THROMBOSIS
ANGIOTENSIN-II REGULATES THE EXPRESSION OF PLASMINOGEN-ACTIVATOR INHIBITOR-1 IN CULTURED ENDOTHELIAL-CELLS - A POTENTIAL LINK BETWEEN THE RENIN-ANGIOTENSIN SYSTEM AND THROMBOSIS
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DOI：
10.1172/jci117809
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发表时间：
1995-03-01
影响因子：
15.9
通讯作者：
TONG, K
中科院分区：
文献类型：
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作者：
VAUGHAN, DE;LAZOS, SA;TONG, K
纤溶酶原激活剂抑制剂 C-1 (PAI-1) 在纤维蛋白溶解调节中发挥着关键作用，是组织型纤溶酶原激活剂的主要抑制剂。 PAI-1 水平升高是心肌梗死复发的危险因素，并且在动脉粥样硬化的人类动脉中局部表达 PAI-1 表达增加。最近的研究表明，使用血管紧张素转换酶抑制剂可以降低特定患者复发心肌梗塞的风险。由于血管紧张素 II (Ang II) 据报道可诱导培养的星形胶质细胞中 PAI-1 的产生，因此我们假设可能有助于血管紧张素转换酶抑制剂产生有益作用的一种机制是对纤溶平衡的影响。在本研究中，我们研究了 Ang II 与培养的牛主动脉内皮细胞 (BAEC) 的相互作用以及该肽对 PAI-1 产生的影响。 I-125-Ang II nas 被发现以可饱和且特异的方式与 BAEC 结合，每毫克蛋白质的表观 K-d 为 1.4 nM，B-max 为 74 fmol。 BAEC 暴露于 Ang II 会诱导培养基中 PAI-1 抗原和 PAI-1 mRNA 水平呈剂量依赖性增加。用 Dup 753 或 [Sar(1), Ile(8)]-Ang II 预处理 BAEC 不会抑制 Ang II 对 PAI-1 mRNA 表达的诱导，这些药物已知可有效竞争与两种主要血管紧张素受体亚型的结合。这些数据表明，Ang II 调节培养的内皮细胞中 PAI-1 的表达，并且这种反应是通过药理学上不同形式的血管紧张素受体介导的。
Plasminogen activator-inhibitor C-1 (PAI-1) plays a critical role in the regulation of fibrinolysis, serving as the primary inhibitor of tissue-type plasminogen activator. Elevated levels of PAI-1 are a risk factor for recurrent myocardial infarction, and locally increased PAI-1 expression has been described in atherosclerotic human arteries. Recent studies have shown that the administration of angiotensin converting enzyme inhibitors reduces the risk of recurrent myocardial infarction in selected patients. Since angiotensin II (Ang II) has been reported to induce PAI-1 production in cultured astrocytes, we have hypothesized that one mechanism that may contribute to the beneficial effect of angiotensin converting enzyme inhibitors is an effect on fibrinolytic balance. In the present study, we examined the interaction of Ang II with cultured bovine aortic endothelial cells (BAECs) and the effects of this peptide on the production of PAI-1. I-125-Ang II nas found to bind to BAECs in a saturable and specific manner, with an apparent K-d of 1.4 nM and B-max of 74 fmol per mg of protein. Exposure of BAECs to Ang II induced dose-dependent increases in PAI-1 antigen in the media and in PAI-1 mRNA levels. Induction of PAI-1 mRNA expression by Ang II was not inhibited by pretreating BAECs with either Dup 753 or [Sar(1), Ile(8)]-Ang II, agents that are known to compete effectively for binding to the two major angiotensin receptor subtypes. These data indicate that Ang II regulates the expression of PAI-1 in cultured endothelial cells and that this response is mediated via a pharmacologically distinct form of the angiotensin receptor.