Experimental Cardiovascular Research Unit, Clinical Research Center, Department of Clinical Sciences, Jan Waldenströms gata 35, CRC 91:12, Lund University, and the Clinical Research Unit, Acute Medical Center, Skåne University Hospital, SE-20502 Malmö, Sweden.
Stroke. 2012 Dec;43(12):3305-12. doi: 10.1161/STROKEAHA.112.664094. Epub 2012 Nov 13.
Recently, plasma soluble urokinase plasminogen activator receptor (suPAR) has gained interest as a marker of cardiovascular risk. suPAR is released through the cleavage of urokinase plasminogen activator receptor (uPAR), which is found in monocytes, activated T-lymphocytes and endothelial cells, all involved in atherosclerosis. suPAR levels have been well studied in plasma, but no studies have focused on suPAR in human atherosclerotic plaques. The aim of this study was to determine whether suPAR measured in the plaque is associated with symptomatic plaques and plaque inflammation.
Plasma and carotid plaques from 162 patients were analyzed. Lipids, collagen, uPAR, and macrophages were measured histologically. Cytokines and suPAR were measured in homogenized plaque extracts using multiplex immunoassay and ELISA, respectively. Plasma levels of suPAR were analysed with ELISA. CD3, CD4, as well as uPAR mRNA expression were assessed with quantitative real-time polymerase chain reaction in plaque homogenates from 123 patients.
Plaque and plasma suPAR levels were higher in symptomatic patients compared with asymptomatic patients. Plaque suPAR levels correlated with plaque content of lipids and macrophages and with proinflammatory chemokines and cytokines monocyte chemoattractant protein 1, tumor necrosis factor α, interleukin 1β, interleukin 6, platelet-derived growth factor AB/BB, monocyte inflammatory protein 1β, regulated on activation normal T-cell expressed and secreted, and s-CD40L. uPAR mRNA and histological staining for uPAR correlated with plaque content of suPAR.
This study shows that suPAR in human carotid plaques and plasma is associated with the presence of symptoms and that plaque suPAR is associated with the vulnerable inflammatory plaque. These findings strengthen the hypothesis of suPAR as a future marker of vulnerable atherosclerotic plaques.
近期，血浆可溶性尿激酶型纤溶酶原激活物受体（suPAR）作为心血管风险标志物受到关注。suPAR 通过尿激酶型纤溶酶原激活物受体（uPAR）的裂解释放，uPAR 存在于单核细胞、活化 T 淋巴细胞和内皮细胞中，而这些细胞均与动脉粥样硬化有关。suPAR 水平在血浆中已得到广泛研究，但尚无研究关注人动脉粥样硬化斑块中的 suPAR。本研究旨在确定斑块中测得的 suPAR 是否与有症状斑块和斑块炎症有关。
分析了 162 例患者的血浆和颈动脉斑块。组织学检测斑块中的脂质、胶原、uPAR 和巨噬细胞。使用多重免疫分析法和 ELISA 分别在匀浆斑块提取物中检测细胞因子和 suPAR。通过 ELISA 分析血浆 suPAR 水平。采用定量实时聚合酶链反应检测 123 例患者斑块匀浆中的 CD3、CD4 以及 uPAR mRNA 表达。
与无症状患者相比，有症状患者的斑块和血浆 suPAR 水平更高。斑块 suPAR 水平与斑块脂质和巨噬细胞含量以及促炎趋化因子和细胞因子单核细胞趋化蛋白 1、肿瘤坏死因子-α、白细胞介素 1β、白细胞介素 6、血小板衍生生长因子 AB/BB、单核细胞炎性蛋白 1β、调节激活正常 T 细胞表达和分泌因子以及 s-CD40L 相关。uPAR mRNA 和 uPAR 组织学染色与斑块 suPAR 含量相关。
本研究表明，人颈动脉斑块和血浆中的 suPAR 与症状的存在有关，且斑块 suPAR 与易损性炎症斑块有关。这些发现进一步支持了 suPAR 作为易损性动脉粥样硬化斑块未来标志物的假说。
