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识别年轻人高血压的尿肽组学特征:非洲 PREDICT 研究:尿肽组学与高血压:尿肽组学与高血压。

Identifying a urinary peptidomics profile for hypertension in young adults: The African-PREDICT study: Urinary peptidomics and hypertension: Urinary peptidomics and hypertension.

机构信息

Hypertension in Africa Research Team (HART), North-West University (Potchefstroom Campus), Potchefstroom, South Africa.

MRC Research Unit for Hypertension and Cardiovascular Disease, North-West University, Potchefstroom, South Africa.

出版信息

Proteomics. 2023 Jun;23(11):e2200444. doi: 10.1002/pmic.202200444. Epub 2023 Apr 3.

Abstract

Hypertension is one of the most important and complex risk factors for cardiovascular diseases (CVDs). By using urinary peptidomics analyses, we aimed to identify peptides associated with hypertension, building a framework for future research towards improved prediction and prevention of premature development of CVD. We included 78 hypertensive and 79 normotensive participants from the African-PREDICT study (aged 20-30 years), matched for sex (51% male) and ethnicity (49% black and 51% white). Urinary peptidomics data were acquired using capillary-electrophoresis-time-of-flight-mass-spectrometry. Hypertension-associated peptides were identified and combined into a support vector machine-based multidimensional classifier. When comparing the peptide data between the normotensive and hypertensive groups, 129 peptides were nominally differentially abundant (Wilcoxon p < 0.05). Nonetheless, only three peptides, all derived from collagen alpha-1(III), remained significantly different after rigorous adjustments for multiple comparisons. The 37 most significant peptides (all p ≤ 0.001) served as basis for the development of a classifier, with 20 peptides being combined into a unifying score, resulting in an AUC of 0.85 in the ROC analysis (p < 0.001), with 83% sensitivity at 80% specificity. Our study suggests potential value of urinary peptides in the classification of hypertension, which could enable earlier diagnosis and better understanding of the pathophysiology of hypertension and premature cardiovascular disease development.

摘要

高血压是心血管疾病(CVD)最重要和最复杂的危险因素之一。通过使用尿肽组学分析,我们旨在鉴定与高血压相关的肽,为未来研究改善 CVD 过早发展的预测和预防奠定基础。我们纳入了来自非洲预测研究(年龄 20-30 岁)的 78 名高血压患者和 79 名血压正常者,按性别(51%为男性)和种族(49%为黑人,51%为白人)匹配。使用毛细管电泳-飞行时间质谱法获得尿肽组学数据。鉴定与高血压相关的肽,并将其组合成基于支持向量机的多维分类器。在比较血压正常组和高血压组的肽数据时,有 129 个肽被鉴定为名义上差异丰富(Wilcoxon p<0.05)。然而,经过严格的多重比较调整后,只有三个肽(均来自胶原蛋白 alpha-1(III))仍然存在显著差异。前 37 个最显著的肽(所有 p ≤ 0.001)作为分类器的基础,其中 20 个肽被组合成一个统一的评分,在 ROC 分析中 AUC 为 0.85(p<0.001),特异性为 80%时的敏感度为 83%。我们的研究表明尿肽在高血压分类中的潜在价值,可以实现更早的诊断和更好地理解高血压和过早心血管疾病发展的病理生理学。

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