Pediatric and Adult Congenital IRCCS, Policlinico San Donato, I-20097 San Donato Milanese, MI, Italy.
Neonatal Intensive Care Unit, Azienda Ospedaliera Universitaria, University of Cagliari, S.P. n° 8, Km 0.700, I-09042 Monserrato, CA, Italy.
Molecules. 2021 Jul 12;26(14):4220. doi: 10.3390/molecules26144220.
Bicuspid aortic valve (BAV) is the most common congenital heart defect responsible for valvular and aortic complications in affected patients. Causes and mechanisms of this pathology are still elusive and thus the lack of early detection biomarkers leads to challenges in its diagnosis and prevention of associated cardiovascular anomalies. The aim of this study was to explore the potential use of urine Nuclear Magnetic Resonance (NMR) metabolomics to evaluate a molecular fingerprint of BAV. Both multivariate and univariate statistical analyses were performed to compare the urinary metabolome of 20 patients with BAV with that of 24 matched controls. Orthogonal partial least squared discriminant analysis (OPLS-DA) showed statistically significant discrimination between cases and controls, suggesting seven metabolites (3-hydroxybutyrate, alanine, betaine, creatine, glycine, hippurate, and taurine) as potential biomarkers. Among these, glycine, hippurate and taurine individually displayed medium sensitivity and specificity by receiver operating characteristic (ROC) analysis. Pathway analysis indicated two metabolic pathways likely perturbed in BAV subjects. Possible contributions of gut microbiota activity and energy imbalance are also discussed. These results constitute encouraging preliminary findings in favor of the use of urine-based metabolomics for early diagnosis of BAV.
二叶式主动脉瓣（BAV）是最常见的先天性心脏缺陷，可导致受影响患者的瓣膜和主动脉并发症。这种病理学的原因和机制仍不清楚，因此缺乏早期检测生物标志物导致其诊断和相关心血管异常的预防面临挑战。本研究旨在探讨尿液核磁共振（NMR）代谢组学在评估 BAV 分子特征方面的潜在用途。我们进行了多元和单变量统计分析，以比较 20 例 BAV 患者和 24 例匹配对照的尿液代谢组。正交偏最小二乘判别分析（OPLS-DA）显示病例和对照组之间存在统计学上显著的区分，提示七种代谢物（3-羟基丁酸、丙氨酸、甜菜碱、肌酸、甘氨酸、马尿酸和牛磺酸）可能作为潜在的生物标志物。其中，甘氨酸、马尿酸和牛磺酸的个体通过接收者操作特征（ROC）分析显示出中等的灵敏度和特异性。途径分析表明，在 BAV 患者中可能存在两种代谢途径受到干扰。还讨论了肠道微生物群活动和能量失衡的可能贡献。这些结果构成了支持使用基于尿液的代谢组学进行 BAV 早期诊断的令人鼓舞的初步发现。
