The proteomic fingerprint in infants with single ventricle heart disease in the interstage period: evidence of chronic inflammation and widespread activation of biological networks.
Front Pediatr
; 11: 1308700, 2023.
Article
de En
| MEDLINE
| ID: mdl-38143535
ABSTRACT
Introduction:
Children with single ventricle heart disease (SVHD) experience significant morbidity across systems and time, with 70% of patients experiencing acute kidney injury, 33% neurodevelopmental impairment, 14% growth failure, and 5.5% of patients suffering necrotizing enterocolitis. Proteomics is a method to identify new biomarkers and mechanisms of injury in complex physiologic states.Methods:
Infants with SVHD in the interstage period were compared to similar-age healthy controls. Serum samples were collected, stored at -80°C, and run on a panel of 1,500 proteins in single batch analysis (Somalogic Inc., CO). Partial Least Squares-Discriminant Analysis (PLS-DA) was used to compare the proteomic profile of cases and controls and t-tests to detect differences in individual proteins (FDR <0.05). Protein network analysis with functional enrichment was performed in STRING and Cytoscape.Results:
PLS-DA readily discriminated between SVHD cases (n = 33) and controls (n = 24) based on their proteomic pattern alone (Accuracy = 0.96, R2 = 0.97, Q2 = 0.80). 568 proteins differed between groups (FDR <0.05). We identified 25 up-regulated functional clusters and 13 down-regulated. Active biological systems fell into six key groups angiogenesis and cell proliferation/turnover, immune system activation and inflammation, altered metabolism, neural development, gastrointestinal system, and cardiac physiology and development.Conclusions:
We report a clear differentiation in the circulating proteome of patients with SVHD and healthy controls with >500 circulating proteins distinguishing the groups. These proteomic data identify widespread protein dysregulation across multiple biologic systems with promising biological plausibility as drivers of SVHD morbidity.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Langue:
En
Journal:
Front Pediatr
Année:
2023
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique