Serum and Urine Thioflavin-T-Enhanced Fluorescence in Severe Preeclampsia.
Serum and Urine Thioflavin-T-Enhanced Fluorescence in Severe Preeclampsia.
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DOI：
10.1161/hypertensionaha.118.11034
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发表时间：
2018-06
期刊：
影响因子：
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通讯作者：
Buhimschi IA
中科院分区：
文献类型：
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作者：
Millen KR;Buhimschi CS;Zhao G;Rood KM;Tabbah S;Buhimschi IA
淀粉样蛋白毒性聚集体的共同特征是能够结合刚果红（嗜红性）并诱导硫黄素-T（ThT）的荧光。基于先前发现患有先兆子痫的妇女表现出尿嗜酸性粒细胞增多症，我们提出存在于尿中的淀粉样蛋白聚集体也在血流中循环，并且该特征与疾病严重程度和临床表型相关。研究了217对来自具有重度先兆子痫特征的妇女的血清和尿液样本中ThT荧光（sPE，n=101，中位[IQR]胎龄（GA）：32 [29-35]周），轻度先兆子痫特征（mPE，n=22，GA：36 [36-37]周）、慢性高血压（crHTN，n=15，GA：38 [37-39]周）、健康妊娠对照（n=57，GA：39 [38-39]周）和非妊娠对照（n=22）。在相同的样本中测量归因于晚期糖基化终产物（AGE）的血清和尿液荧光，并校正自发荧光。有没有GA相关的变化，ThT荧光，虽然近期血清ThT荧光增加相比，非妊娠状态。与健康妊娠对照相比，sPE中的血清和尿液ThT荧光增加（两者均为P<0.001），但mPE或crHTN中没有。除crHTN外，血清或尿液的AGE相关荧光与对照组无差异。与尿液或血清ThT荧光相比，尿液嗜中性粒细胞增多症与PE严重程度的关系更强。然而，血清ThT荧光与HELLP综合征的临床特征独立相关（P=0.003）。我们证明，ThT荧光，淀粉样蛋白聚集体的标志物，是增加妇女血清PE和可能是由于其细胞毒性与HELLP综合征。
Common features of amyloid-like proteotoxic aggregates are the ability to bind Congo red (congophilia) and to induce fluorescence of Thioflavin-T (ThT). Based on prior discovery that women with preeclampsia exhibit urine congophilia, we proposed that amyloid-like protein aggregates present in urine also circulate in the blood stream and this feature is linked to disease severity and clinical phenotype. ThT fluorescence was investigated in 217 paired serum and urine samples from women with severe features of preeclampsia (sPE, n=101, median [IQR] gestational age (GA): 32 [29-35] weeks), mild features of preeclampsia (mPE, n=22, GA: 36 [36-37] weeks), chronic hypertension (crHTN, n=15, GA: 38 [37-39] weeks), healthy pregnant controls (n=57, GA: 39 [38-39] weeks), and non-pregnant controls (n=22). Serum and urine fluorescence attributable to advanced glycation end-products (AGE) was measured in the same samples with correction for auto-fluorescence. There were no GA-related changes in ThT fluorescence, although near-term serum ThT fluorescence increased compared to non-pregnant state. Compared to healthy pregnant controls, serum and urine ThT fluorescence was increased in sPE (P<0.001 for both) but not in mPE or crHTN. Except for crHTN, AGE-related fluorescence of serum or urine did not differ from controls. Urine congophilia had a stronger relationship with PE severity compared to either urine or serum ThT fluorescence. However, serum ThT fluorescence was independently associated with clinical features of HELLP syndrome (P=0.003). We demonstrate that ThT fluorescence, a marker of amyloid-like aggregates, is increased in serum of women with PE and likely due to their cytotoxicity associated with HELLP syndrome.