Valias Gabriela Ribeiro, Gomes Patricia Rodrigues Lourenço, Amaral Fernanda G, Alnuaimi Saif, Monteiro Daniela, O'Sullivan Siobhán, Zangaro Renato, Cipolla-Neto José, Acuna Juan, Baltatu Ovidiu Constantin, Campos Luciana Aparecida
Center of Innovation, Technology and Education (CITE) at Anhembi Morumbi University-Anima Institute, Sao Jose dos Campos Technology Park, Sao Jose dos Campos, Brazil.
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Front Mol Biosci. 2022 Mar 2;9:800638. doi: 10.3389/fmolb.2022.800638. eCollection 2022.
A large research portfolio indicates that an activated renal renin-angiotensin system or a deficit on melatonin is associated with several cardiovascular pathologies. In this observational clinical study, we hypothesized that alterations in urinary melatonin or angiotensinogen levels may be altered in two common conditions, preeclampsia and gestational diabetes. Our study's primary objective was to assess melatonin and angiotensinogen as novel disease biomarkers detectable and quantifiable in the urine of pregnant women with or without pregnancy complications. This was a concurrent cohort study of pregnant women with selected obstetric pathologies (gestational diabetes, preeclampsia, hypertension and obesity with hypertension). A group of healthy controls was also included. Urinary 6-sulfatoxymelatonin and angiotensinogen were measured by sensitive and specific ELISAs in first morning void urine samples. The patients were included in the cohort consecutively, and the diagnosis was blinded at the level of urine collection. Urinary 6-sulfatoxymelatonin and angiotensinogen levels were investigated in the patients included in the cohort. Urinary levels of angiotensinogen were significantly higher in the gestational diabetes [angiotensinogen/creatinine ratio median (25th, 75th): 0.11 (0.07, 0.18)] and preeclampsia [0.08 (0.06, 0.18)] groups than in those with healthy pregnancy [0.05(0.04, 0.06]; 6-sulfatoxymelatonin levels were significantly lower in the gestational diabetes [ug/h: median (25th, 75th): 0.12(0.08, 0.17)] and preeclampsia [0.12 (0.09, 0.15)] groups than in those with healthy pregnancy [0.20 (0.15, 0.27]. Neither morning void protein/creatinine ratio nor 24-h urine protein estimate were significantly different between the study groups. These results suggest that urinary angiotensinogen levels may indicate an intrarenal RAS activation while melatonin production appears to be defective in gestational diabetes or hypertension. An angiotensinogen/melatonin ratio is suggested as an early biomarker for identification of gestational diabetes or hypertension. This report provides a basis for the potential use of melatonin for the treatment of preeclampsia. A prospective study in a larger number of patients to determine the operative characteristics of these markers as potential diagnostic tests is justified.
大量的研究项目表明，激活的肾素 - 血管紧张素系统或褪黑素缺乏与多种心血管疾病相关。在这项观察性临床研究中，我们假设在两种常见情况，即先兆子痫和妊娠期糖尿病中，尿褪黑素或血管紧张素原水平可能会发生改变。我们研究的主要目的是评估褪黑素和血管紧张素原，作为在有或无妊娠并发症的孕妇尿液中可检测和量化的新型疾病生物标志物。这是一项对患有特定产科疾病（妊娠期糖尿病、先兆子痫、高血压以及肥胖伴高血压）的孕妇进行的同期队列研究。还纳入了一组健康对照。通过灵敏且特异的酶联免疫吸附测定法（ELISA）对首次晨尿样本中的尿6 - 硫酸氧褪黑素和血管紧张素原进行检测。患者连续纳入队列，在尿液收集阶段对诊断进行设盲。对队列中的患者研究尿6 - 硫酸氧褪黑素和血管紧张素原水平。妊娠期糖尿病组[血管紧张素原/肌酐比值中位数（第25百分位数，第75百分位数）：0.11（0.07，0.18）]和先兆子痫组[0.08（0.06，0.18）]的尿血管紧张素原水平显著高于正常妊娠组[0.05（0.04，0.06）]；妊娠期糖尿病组[微克/小时：中位数（第25百分位数，第75百分位数）：0.12（0.08，0.17）]和先兆子痫组[0.12（0.09，0.15）]的6 - 硫酸氧褪黑素水平显著低于正常妊娠组[0.20（0.15，0.27）]。各研究组之间晨尿蛋白/肌酐比值和24小时尿蛋白估计值均无显著差异。这些结果表明，尿血管紧张素原水平可能提示肾内肾素 - 血管紧张素系统（RAS）激活，而在妊娠期糖尿病或高血压中褪黑素生成似乎存在缺陷。建议将血管紧张素原/褪黑素比值作为识别妊娠期糖尿病或高血压的早期生物标志物。本报告为褪黑素潜在用于治疗先兆子痫提供了依据。开展一项针对更多患者的前瞻性研究以确定这些标志物作为潜在诊断检测方法的操作特性是合理的。
