Augmented urokinase receptor expression in atheroma.
Augmented urokinase receptor expression in atheroma.
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动脉粥样硬化中尿激酶受体表达增强。
DOI：
10.1161/01.atv.15.1.37
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Sobel,BE
中科院分区：
文献类型：
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作者：
Noda-Heiny,H;Daugherty,A;Sobel,BE
血管内皮细胞增殖和迁移到新生内膜是动脉粥样硬化形成的标志。然而，对此负责的机制尚未完全阐明。平滑肌细胞增殖和迁移的一个潜在中介是纤溶酶原通过与血管壁内细胞上的受体结合的激活剂来激活。为了确定动脉粥样硬化中的血管平滑肌细胞是否表达尿激酶型纤溶酶原激活物受体(uPA-R)，我们用免疫染色的方法研究了摄入胆固醇的新西兰大白兔和人类受试者的动脉粥样硬化。使用抗uPA-R的单抗，在兔和人动脉粥样硬化病变的新生内膜中均观察到uPA-R的强烈免疫染色。在正常动脉组织中未检测到uPA-R。免疫组织化学染色证实uPA-R定位于巨噬细胞和新生内膜平滑肌细胞。此外，Western blotting显示，动脉粥样硬化提取物中的uPA-R蛋白的含量至少是正常血管提取物的九倍。迁移中的血管平滑肌细胞uPA-R基因表达无明显增加。因此，转录后调控的改变可能是导致uPA-R增加的原因之一。在体外，uPA-R抗体延缓了培养的血管平滑肌细胞的迁移。我们的结果表明，在动脉粥样硬化中，细胞表面uPA-R的增加有助于细胞周围蛋白的降解，从而增加血管平滑肌细胞的迁移，继而增加新生内膜的形成。
Smooth muscle cell proliferation and migration into neointima are hallmarks of atherogenesis. However, mechanisms responsible have not yet been fully elucidated. One potential mediator of both smooth muscle cell proliferation and migration is activation of plasminogen by activators bound to receptors on cells within the vessel wall. To determine whether vascular smooth muscle cells within atheroma express the receptor for urokinase-type plasminogen activator (uPA-R), we characterized atheroma in cholesterol-fed New Zealand White rabbits and human subjects by immunostaining. Intense immunostaining of uPA-R was observed throughout the neointima in both rabbit and human atherosclerotic lesions with the use of a monoclonal antibody to uPA-R. uPA-R was not detectable in normal arterial tissues. uPA-R was localized to macrophages and neointimal smooth muscle cells identified by immunostaining in serial sections. Furthermore, uPA-R protein in extracts from atheroma was present in at least a ninefold greater quantity compared with extracts from normal vessels, as shown by Western blotting. Expression of uPA-R mRNA in migrating vascular smooth muscle cells did not increase significantly. Thus, altered posttranscriptional regulation may be contributing to the increased uPA-R. In vitro, antibodies to uPA-R delayed the migration of cultured vascular smooth muscle cells. Our results suggest that increased cell-surface uPA-R contributes to pericellular proteolysis and consequently increased neointimalization secondary to increased vascular smooth muscle cell migration in atheroma.