Urokinase-type plasminogen activator receptor is associated with macrophages and plaque rupture in symptomatic carotid atherosclerosis.

Urokinase-type plasminogen activator receptor is associated with macrophages and plaque rupture in symptomatic carotid atherosclerosis.
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尿激酶型纤溶酶原激活剂受体与症状性颈动脉粥样硬化中的巨噬细胞和斑块破裂有关。

DOI:
10.3892/ijmm_00000043
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发表时间:
2008
影响因子:
5.4
通讯作者:
B. Fagerberg
B. Fagerberg
中科院分区:
医学3区
文献类型:
--
作者:
P. Svensson;F. Olson;D. Hägg;M. Ryndel;O. Wiklund;L. Karlström;J. Hulthe;L. Carlsson;B. Fagerberg

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在新近出现症状的颈动脉粥样硬化斑块中,巨噬细胞的浸润与斑块的不稳定性有很强的相关性,推测与巨噬细胞相关的机制可能与斑块的易损性和破裂有关。我们先前发现人巨噬细胞高表达尿激酶型纤溶酶原激活物受体(UPAR)。本研究的目的是研究uPAR在有症状的颈动脉斑块中是否与巨噬细胞共定位,以及uPAR的表达是否与斑块破裂有关。实时定量RT-PCR分析显示,与组织板相比,单核细胞来源的巨噬细胞和颈动脉内膜切除术中的uPAR表达水平较高。从12例有症状的患者的颈动脉内膜切除术中制备连续的横切面,用免疫组织化学染色检测uPAR和CD68阳性的巨噬细胞,并与组织病理学评估相结合。在12例有症状的颈动脉内膜切除术中,uPAR与CD68阳性的巨噬细胞共定位,其免疫染色面积之间高度相关(r=0.9,p<0.001)。UPAR和CD68在动脉内膜剥脱术后颈总动脉末端断裂最常见的分叉部周围呈强阳性表达(p<0.05)。破裂斑块切片的uPAR染色程度高于未破裂斑块切片。综上所述,uPAR在单核细胞来源的巨噬细胞和症状性颈动脉斑块中高表达,uPAR与巨噬细胞共定位于颈动脉症状性斑块,uPAR主要见于破裂斑块。这些发现支持这样的假设,即uPAR与症状性动脉粥样硬化病变的斑块破裂有关。
There is a strong correlation between macrophage infiltration and plaque instability in recently symptomatic carotid atherosclerotic plaques, and it is hypothesised that mechanisms related to macrophages may be involved in plaque vulnerability and rupture. We previously found high expression of urokinase-type plasminogen activator receptor (UPAR) in human macrophages. The aim of this study was to investigate whether UPAR co-localises with macrophages in symptomatic carotid plaques, and whether UPAR expression is associated with plaque rupture. Real-time RT-PCR assays showed that UPAR expression levels were high in monocyte-derived macrophages and in carotid endarterectomies compared with a tissue panel. Serial transverse sections were prepared from carotid endarterectomies from 12 symptomatic patients, and analyzed with immunohistochemical staining for UPAR and for CD68-positive macrophages, and with histopathological assessment. UPAR co-localised with CD68-positive macrophages, with a high correlation (r=0.90, p<0.001) between immunostained areas in 12 carotid endarterectomies from symptomatic patients. High degrees of UPAR and CD68 staining were found in sections around the bifurcation level where rupture was most common, while low degrees of staining were found in sections of the common carotid artery end of the endarterectomy (p<0.05). Higher degrees of UPAR staining were observed in ruptured plaque sections compared with non-ruptured sections. In conclusion, UPAR was highly expressed in monocyte-derived macrophages and in symptomatic carotid plaques, UPAR co-localised with macrophages in carotid symptomatic plaques and UPAR was predominantly found in ruptured plaque segments. These findings support the hypothesis that UPAR is related to plaque rupture in symptomatic atherosclerotic lesions.
动脉粥样硬化中尿激酶受体表达增强。
DOI: 10.1161/01.atv.15.1.37
发表时间: 1995
期刊: Arteriosclerosis, thrombosis, and vascular biology
影响因子: --
作者:
Noda-Heiny,H;Daugherty,A;Sobel,BE
通讯作者: Sobel,BE