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通过尿液蛋白质组学预测早产儿心血管风险:一项探索性研究。

Prediction of cardiovascular risk in preterm neonates through urinary proteomics: An exploratory study.

作者信息

Cabral Estela, Soares Henrique, Guimarães Hercília, Vitorino Rui, Ferreira Rita, Henriques-Coelho Tiago

机构信息

School of Health Sciences, University of Minho, Braga, Portugal.

Departmento de Pediatria, Faculdade de Medicina, Universidade do Porto, Porto, Portugal.

出版信息

Porto Biomed J. 2017 Nov-Dec;2(6):287-292. doi: 10.1016/j.pbj.2017.04.002. Epub 2017 Jun 17.

Abstract

HIGHLIGHTS

Urine proteomics allows the identification of the pathways modulated in neonates.Up-regulated pathways in preterm include immunity, metabolism and oxidative stress.Some of these pathways seem to be modulated by the nutritional support.AGT and RBP4 might be related to the development of cardiovascular diseases.

ABSTRACT

Preterm birth has been associated with an increased risk of cardiovascular diseases (CVD) in adulthood. The goal of our study was to give new molecular insights on the relationship between prematurity and CVD risk and to identify putative biomarkers that would facilitate the development of effective screening and therapeutic strategies. In this sense, mass spectrometry (MS)-based proteomics was applied to the characterization of urine protein profile.GeLC-MS/MS analysis of urine (desalted and concentrated with a 10-kDa filter) followed by bioinformatics was applied for the characterization of preterm and full-term neonates. Urine proteome profiling retrieved 434 unique proteins, from which 126 were common to both groups, 37 were unique to preterm and 58 to full-term neonates. Protein-protein interaction analysis for unique proteins and common ones present in significant distinct levels retrieved immune system, metabolism, defense systems and tissue remodeling as the most representative clusters in preterm neonates.Metabolic adaptation along with the up-regulation of heart growth (identified by angiotensinogen and retinol-binding protein 4) may account for an increased CVD risk in preterm neonates. These proteins may have predictive value of CVD in adulthood of this specific group of neonates. The follow-up of urinary proteome dynamics of preterm and full-term neonates will be crucial for the validation of this hypothesis.

摘要

要点

尿液蛋白质组学有助于识别新生儿中被调节的通路。早产儿中上调的通路包括免疫、代谢和氧化应激。其中一些通路似乎受到营养支持的调节。血管紧张素原(AGT)和视黄醇结合蛋白4(RBP4)可能与心血管疾病的发生有关。

摘要

早产与成年后患心血管疾病(CVD)的风险增加有关。我们研究的目的是对早产与CVD风险之间的关系提供新的分子见解,并识别可能有助于开发有效筛查和治疗策略的生物标志物。从这个意义上说,基于质谱(MS)的蛋白质组学被应用于尿液蛋白质谱的表征。对尿液(用10 kDa滤器脱盐和浓缩)进行凝胶液相色谱-串联质谱(GeLC-MS/MS)分析,然后进行生物信息学分析,以表征早产儿和足月儿。尿液蛋白质组分析检索到434种独特的蛋白质,其中126种是两组共有的,37种是早产儿特有的,58种是足月儿特有的。对独特蛋白质和显著不同水平的共有蛋白质进行蛋白质-蛋白质相互作用分析,发现免疫系统、代谢、防御系统和组织重塑是早产儿中最具代表性的簇。代谢适应以及心脏生长的上调(由血管紧张素原和视黄醇结合蛋白4确定)可能是早产儿患CVD风险增加的原因。这些蛋白质可能对这一特定组新生儿成年后患CVD具有预测价值。对早产儿和足月儿尿液蛋白质组动态的随访对于验证这一假设至关重要。

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