Lipoprotein (a) regulates plasminogen activator inhibitor-1 expression in endothelial cells. A potential mechanism in thrombogenesis.
Lipoprotein (a) regulates plasminogen activator inhibitor-1 expression in endothelial cells. A potential mechanism in thrombogenesis.
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DOI：
10.1016/s0021-9258(18)52266-3
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发表时间：
1991-02
期刊：
影响因子：
--
通讯作者：
O. Etingin;D P Hajjar;K. Hajjar;P. Harpel;R L Nachman
中科院分区：
文献类型：
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作者：
O. Etingin;D P Hajjar;K. Hajjar;P. Harpel;R L Nachman
脂蛋白(a) （Lp(a)）是一种低密度脂蛋白样颗粒，含有纤溶酶原样载脂蛋白a。在冠状动脉粥样硬化性疾病患者中，Lp(a)水平升高。最近的研究表明，Lp(a)竞争性地抑制纤溶酶原与内皮细胞的结合，并干扰表面相关纤溶酶的产生。在这项研究中，我们提出了Lp(a)存在于炎症组织微血管的证据。此外，我们证明Lp(a)调节内皮细胞合成一种主要的纤溶蛋白，纤溶酶原激活物抑制剂-1 （PAI-1）。在培养的人内皮细胞中，Lp(a)增强了PAI-1抗原、活性和稳态mRNA水平，而不改变组织纤溶酶原激活物活性或mRNA转录物水平。这种效应是细胞特异性的。虽然其他脂蛋白不能协调地提高内皮细胞中PAI-1 mRNA水平，但低密度脂蛋白处理选择性地提高了PAI-1 3.4千碱基mRNA种类的水平，而不会同时增加PAI-1活性或抗原。内皮细胞暴露于Lp(a)后，由于Lp(a)暴露后组织因子、血小板源性生长因子和白细胞介素-6的功能活性和mRNA水平未升高，因此内皮细胞未引起全局性活化。这些数据提示了一种分子机制，即Lp(a)可能通过增加PAI-1表达来支持特定的血栓形成前内皮细胞表型。
Lipoprotein (a) (Lp(a)) is a low density lipoprotein-like particle which contains the plasminogen-like apolipoprotein a. Lp(a) levels are elevated in patients with atherosclerotic coronary artery disease. Recent studies suggest that Lp(a) competitively inhibits plasminogen binding to the endothelial cell and interferes with surface-associated plasmin generation. In this study, we present evidence for the presence of Lp(a) in the microvasculature of inflamed tissue. In addition, we demonstrate that Lp(a) regulates endothelial cell synthesis of a major fibrinolytic protein, plasminogen activator inhibitor-1 (PAI-1). In cultured human endothelial cells, Lp(a) enhanced PAI-1 antigen, activity, and steady-state mRNA levels without altering tissue plasminogen activator activity or mRNA transcript levels. This effect was cell-specific. Although other lipoproteins did not coordinately raise PAI-1 mRNA levels in endothelial cells, low density lipoprotein treatment selectively raised the level of the 3.4-kilobase mRNA species of PAI-1 without a concomitant increase in PAI-1 activity or antigen. Endothelial cell exposure to Lp(a) did not cause generalized endothelial cell activation since the functional activity and mRNA levels for tissue factor, platelet-derived growth factor and interleukin-6 were not elevated following Lp(a) exposure. These data suggest a molecular mechanism whereby Lp(a) may support a specific prothrombotic endothelial cell phenotype, namely by increasing PAI-1 expression.