INCREASED TYPE-1 PLASMINOGEN-ACTIVATOR INHIBITOR GENE-EXPRESSION IN ATHEROSCLEROTIC HUMAN ARTERIES
INCREASED TYPE-1 PLASMINOGEN-ACTIVATOR INHIBITOR GENE-EXPRESSION IN ATHEROSCLEROTIC HUMAN ARTERIES
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DOI：
10.1073/pnas.89.15.6998
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发表时间：
1992-08-01
影响因子：
11.1
通讯作者：
LOSKUTOFF, DJ
中科院分区：
文献类型：
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作者：
SCHNEIDERMAN, J;SAWDEY, MS;LOSKUTOFF, DJ
纤维蛋白溶解能力的降低被认为通过促进血栓形成和纤维蛋白沉积在发展中的动脉粥样硬化病变内而加速动脉粥样硬化形成的过程。1型纤溶酶原激活物抑制剂（派-1）是组织型纤溶酶原激活物的主要抑制剂，并且已经发现在通常定义为血栓前的许多临床病症中增加。为了研究这种抑制剂在动脉粥样硬化中的潜在作用，我们检测了派-1 mRNA在11个严重病变和5个相对正常的人动脉节段中的表达，这些动脉来自16个不同的患者，这些患者接受了主动脉闭塞性或动脉瘤性疾病的重建手术。RNA（北方）印迹放射自显影的光密度扫描显示派-1 mRNA在严重动脉粥样硬化血管中的水平（平均光密度值为1.7 ± 0.28 SEM）显著高于正常或轻度病变动脉（平均光密度值为0.63 ± 0.09 SEM; P < 0.05）。派-1 mRNA水平与动脉粥样硬化程度密切相关。通过原位杂交分析来自相同患者的相邻组织切片，证实了在动脉粥样硬化动脉的增厚内膜内，主要在斑块的基底周围，有大量派-1 mRNA阳性细胞。派-1 mRNA在坏死组织内的散在细胞和外膜血管内皮细胞中也有表达。与这些结果相反，派-1 mRNA主要在正常主动脉组织的管腔内皮细胞内可见。我们的数据为派-1 mRNA在严重动脉粥样硬化的人动脉中的表达增加提供了初步证据，并表明派-1在人类动脉粥样硬化疾病的进展中发挥作用。
Decreased fibrinolytic capacity has been suggested to accelerate the process of arterial atherogenesis by facilitating thrombosis and fibrin deposition within developing atherosclerotic lesions. Type 1 plasminogen activator inhibitor (PAI-1) is the primary inhibitor of tissue-type plasminogen activator and has been found to be increased in a number of clinical conditions generally defined as prothrombotic. To investigate the potential role of this inhibitor in atherosclerosis, we examined the expression of PAI-1 mRNA in segments of 11 severely diseased and 5 relatively normal human arteries obtained from 16 different patients undergoing reconstructive surgery for aortic occlusive or aneurysmal disease. Densitometric scanning of RNA (Northern) blot autoradiograms revealed significantly increased levels of PAI-1 mRNA in severely atherosclerotic vessels (mean densitometric value, 1.7 +/- 0.28 SEM) compared with normal or mildly affected arteries (mean densitometric value, 0.63 +/- 0.09 SEM; P < 0.05). In most instances, the level of PAI-1 mRNA was correlated with the degree of atherosclerosis. Analysis of adjacent tissue sections from the same patients by in situ hybridization demonstrated an abundance of PAI-1 mRNA-positive cells within the thickened intima of atherosclerotic arteries, mainly around the base of the plaque. PAI-1 mRNA could also be detected in cells scattered within the necrotic material and in endothelial cells of adventitial vessels. In contrast to these results, PAI-1 mRNA was visualized primarily within luminal endothelial cells of normal-appearing aortic tissue. Our data provide initial evidence for the increased expression of PAI-1 mRNA in severely atherosclerotic human arteries and suggest a role for PAI-1 in the progression of human atherosclerotic disease.