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

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.

Keywords: Cardiovascular diseases; GeLC–MS/MS; Low birth weight; Neonates; Urine.

Fig. 1.

Venn diagram representing the distribution of identified peptides per group evidencing the overlapped and unique peptides.

Fig. 2.

Normalized abundance of urinary proteins in PreTerm vs. Term groups. Protein accession number has correspondence to protein name at Supplemental Table S1.

Fig. 3.

ClueGo and CluePedia analysis of protein-protein interaction considering unique proteins per group and common proteins present in significant distinct levels (based on emPAI values) in the urine of neonates from Term and PreTerm groups. Green nodes refer to biological processes positively regulated in preterm neonates whereas red nodes refer to the ones widespread in term neonates. As can be depicted, immune response, negative regulation of endopeptidase activity, regulation of defense response, ion homeostasis and catabolic processes are biological processes prevalent in preterm neonates.