Elevated expression of urokinase plasminogen activator in rodent models and patients with cerebral amyloid angiopathy.
Elevated expression of urokinase plasminogen activator in rodent models and patients with cerebral amyloid angiopathy.
复制标题
啮齿动物模型和脑淀粉样血管病患者中尿激酶纤溶酶原激活剂的表达升高。
DOI：
10.1111/nan.12804
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发表时间：
2022
影响因子：
5
通讯作者：
Klijn,
中科院分区：
文献类型：
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作者：
Vervuurt,Marc;Zhu,Xiaoyue;Schrader,Joseph;deKort,AnnaM;Marques,TaináM;Kersten,Iris;PetersvanTon,AnnemiekeM;Abdo,WilsonF;Schreuder,FlorisHBM;Rasing,Ingeborg;Terwindt,GiselaM;Wermer,MariekeJH;Greenberg,StevenM;Klijn,
目的研究尿激酶型纤溶酶原激活物（uPA）与脑淀粉样血管病（CAA）发生、发展的关系。材料和方法采用定量聚合酶链反应（qPCR）和免疫组织化学方法研究rTg‐DI大鼠脑血管uPA mRNA表达和uPA与β淀粉样蛋白（Aβ）共定位。sCAA）患者和对照受试者。使用酶联免疫吸附试验（ELISA）测定rTg‐DI和WT大鼠以及两个单独的sCAA和荷兰型遗传性CAA（D‐CAA）患者和对照组的脑脊液（CSF）uPA水平。结果在rTg‐DI大鼠和sCAA患者的脑血管中明确检测到uPA的存在，但在WT大鼠或非CAA人类对照组中未检测到。uPA表达与微血管Aβ沉积高度共定位。在rTg‐DI大鼠中，与WT大鼠相比，uPA mRNA表达在3月龄时高度升高（与微血管Aβ沉积的出现一致），并持续至12月龄（伴有重度微血管CAA沉积）。与WT大鼠相比，rTg‐DI大鼠的CSF uPA水平升高（p= 0.03），与对照组相比，sCAA患者的CSF uPA水平升高（校正受试者年龄后，p= 0.05和p = 0.03）。在无症状和有症状的D-CAA患者及其各自的对照组之间未发现CSF uPA水平的差异（经年龄调整后，p= 0.09和p = 0.44）。CAA中脑血管uPA表达增加与rTg‐DI大鼠和人CAA患者CSF uPA量增加相关，表明uPA可作为CAA的生物标志物。
AimsThe aim of this work is to study the association of urokinase plasminogen activator (uPA) with development and progression of cerebral amyloid angiopathy (CAA).Materials and methodsWe studied the expression of uPA mRNA by quantitative polymerase chain reaction (qPCR) and co‐localisation of uPA with amyloid‐β (Aβ) using immunohistochemistry in the cerebral vasculature of rTg‐DI rats compared with wild‐type (WT) rats and in a sporadic CAA (sCAA) patient and control subject using immunohistochemistry. Cerebrospinal fluid (CSF) uPA levels were measured in rTg‐DI and WT rats and in two separate cohorts of sCAA and Dutch‐type hereditary CAA (D‐CAA) patients and controls, using enzyme‐linked immunosorbent assays (ELISA).ResultsThe presence of uPA was clearly detected in the cerebral vasculature of rTg‐DI rats and an sCAA patient but not in WT rats or a non‐CAA human control. uPA expression was highly co‐localised with microvascular Aβ deposits. In rTg‐DI rats, uPA mRNA expression was highly elevated at 3 months of age (coinciding with the emergence of microvascular Aβ deposition) and sustained up to 12 months of age (with severe microvascular CAA deposition) compared with WT rats. CSF uPA levels were elevated in rTg‐DI rats compared with WT rats (p= 0.03), and in sCAA patients compared with controls (after adjustment for age of subjects,p= 0.05 andp= 0.03). No differences in CSF uPA levels were found between asymptomatic and symptomatic D‐CAA patients and their respective controls (after age‐adjustment,p= 0.09 andp= 0.44). Increased cerebrovascular expression of uPA in CAA correlates with increased quantities of CSF uPA in rTg‐DI rats and human CAA patients, suggesting that uPA could serve as a biomarker for CAA.