Exosome-Enriched Plasma Analysis as a Tool for the Early Detection of Hypertensive Gestations.

Exosome-Enriched Plasma Analysis as a Tool for the Early Detection of Hypertensive Gestations.
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DOI:
10.3389/fphys.2021.767112
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发表时间:
2021
影响因子:
4
通讯作者:
Borbely AU
Borbely AU
中科院分区:
医学2区
文献类型:
--
作者:
Weingrill RB;Paladino SL;Souza MLR;Pereira EM;Marques ALX;Silva ECO;da Silva Fonseca EJ;Ursulino JS;Aquino TM;Bevilacqua E;Urschitz J;Silva JC;Borbely AU

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妊娠高血压疾病与早产、死产以及产妇发病率和死亡率密切相关。妊娠期高血压疾病 (HDP) 通常在妊娠 20 周后发病,这限制了早期干预。胎盘通过释放细胞外囊泡(尤其是外泌体)等机制进行通信,直接负责调节局部和全身生理机能。在这项研究中,我们假设对富含外泌体的母体血浆进行分析可以为妊娠早期诊断 HDP 提供更有针对性和更适用的方法。因此,在妊娠第20周至第24周期间收集了24名孕妇(11名对照者,13名HDP)的外周血浆,并离心进行外泌体富集。通过拉曼光谱和质子核磁共振代谢组学 (1H NMR) 分析富含外泌体的血浆样品。主成分分析 (PCA) 和正交偏最小二乘判别分析 (OPLS-DA) 用于分析 600–1,800 cm–1 光谱区域的拉曼数据,以确定其区分不同组的潜力。使用主成分分析,我们能够区分这两个组,89% 的方差都存在于前三个主成分中。在 HDP 患者中,鞘磷脂、乙酰辅酶 A、蛋氨酸、DNA、RNA、苯丙氨酸、色氨酸、类胡萝卜素、酪氨酸、精氨酸、亮氨酸、酰胺 I 和 III 以及磷脂的拉曼带强度存在最显着差异。 1H NMR 分析显示 HDP 中的 D-葡萄糖、L-脯氨酸、L-酪氨酸、甘氨酸和鹅氨酸水平降低,而 2-羟基戊酸、多不饱和脂肪酸和极低密度脂蛋白 (VLDL) 水平升高。 1 H NMR 结果能够将未知样品分配到对照组或 HDP 组,使用正交偏最小二乘判别分析的精度为 88.3%,使用逻辑回归分析的精度为 87%。我们的结果表明,对富含外泌体的血浆进行分析可以对母胎界面处的胎盘功能进行初步评估,并有助于 HDP 的诊断、预后和治疗,以及检测 HDP 的新型早期生物标志物。
Hypertensive disorders of pregnancy are closely associated with prematurity, stillbirth, and maternal morbidity and mortality. The onset of hypertensive disorders of pregnancy (HDP) is generally noticed after the 20th week of gestation, limiting earlier intervention. The placenta is directly responsible for modulating local and systemic physiology by communicating using mechanisms such as the release of extracellular vesicles, especially exosomes. In this study, we postulated that an analysis of exosome-enriched maternal plasma could provide a more focused and applicable approach for diagnosing HDP earlier in pregnancy. Therefore, the peripheral blood plasma of 24 pregnant women (11 controls, 13 HDP) was collected between 20th and 24th gestational weeks and centrifuged for exosome enrichment. Exosome-enriched plasma samples were analyzed by Raman spectroscopy and by proton nuclear magnetic resonance metabolomics (1H NMR). Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to analyze the Raman data, from the spectral region of 600–1,800 cm–1, to determine its potential to discriminate between groups. Using principal component analysis, we were able to differentiate the two groups, with 89% of all variances found in the first three principal components. In patients with HDP, most significant differences in Raman bands intensity were found for sphingomyelin, acetyl CoA, methionine, DNA, RNA, phenylalanine, tryptophan, carotenoids, tyrosine, arginine, leucine, amide I and III, and phospholipids. The 1H NMR analysis showed reduced levels of D-glucose, L-proline, L-tyrosine, glycine, and anserine in HDP, while levels of 2-hydroxyvalerate, polyunsaturated fatty acids, and very-low-density lipoprotein (VLDL) were increased. 1H NMR results were able to assign an unknown sample to either the control or HDP groups at a precision of 88.3% using orthogonal partial least squares discriminant analysis and 87% using logistic regression analysis. Our results suggested that an analysis of exosome-enriched plasma could provide an initial assessment of placental function at the maternal-fetal interface and aid HDP diagnosis, prognosis, and treatment, as well as to detect novel, early biomarkers for HDP.
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发表时间: 2002-12-01
期刊: CLINICAL SCIENCE
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作者:
Jackson, AA;Dunn, RL;Langley-Evans, SC
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