Related Experiment Video

Updated: Feb 14, 2026

An Integrated Workflow of Identification and Quantification on FDR Control-Based Untargeted Metabolome
05:35

An Integrated Workflow of Identification and Quantification on FDR Control-Based Untargeted Metabolome

Published on: September 20, 2022

4.3K

Untargeted Serum Proteomics in the Fontan Circulation Reveals Three Distinct Molecular Signatures of Fontan

Alexander Blaha1, David Renaud1, Fatima Ageed1

  • 1Department of Child and Adolescent Health, Division of Pediatrics III-Cardiology, Pulmonology, Allergology and Cystic Fibrosis, Medical University of Innsbruck, 6020 Innsbruck, Austria.

International Journal of Molecular Sciences
|February 13, 2026
PubMed

Insights

This study reveals novel molecular differences in Fontan procedure patients, identifying potential biomarkers like CYB5R3 and altered extracellular matrix organization. These findings offer insights into Fontan circulation complexity for improved risk stratification and therapies.

Area of Science:

  • Cardiovascular Proteomics
  • Congenital Heart Disease Research
  • Systems Biology in Medicine

Background:

  • The Fontan procedure, a palliative treatment for single-ventricle congenital heart disease, improves survival but leads to long-term complications.
  • Previous proteomic studies in Fontan patients were limited to adults, targeted panels, or methodological comparisons.
  • Systemic molecular changes in younger, diverse Fontan patient populations remain poorly understood.

Purpose of the Study:

  • To characterize systemic molecular alterations in younger Fontan procedure patients using untargeted proteomics.
  • To identify potential biomarkers for risk stratification and therapeutic targets in Fontan-associated complications.
  • To explore novel pathways involved in the pathophysiology of the Fontan circulation.

Main Methods:

  • Serum samples from 48 Fontan patients and 48 healthy controls were analyzed using mass spectrometry with TMT labeling.
  • Quantification of 2228 proteins, with 124 found to be significantly differentially abundant (FC > 1.5 or <0.67, FDR-adjusted p < 0.05).
  • Network analysis to identify functional clusters and stratified analyses for high-risk patients.

Main Results:

  • Network analysis revealed altered extracellular matrix (ECM) organization (increased), actin cytoskeleton organization (decreased), and platelet pathways (decreased).
  • High-risk Fontan patients exhibited reduced ECM protein abundance, suggesting a shift towards fibrosis.
  • Uniquely elevated cytochrome b5 reductase 3 (CYB5R3) was observed, indicating altered redox homeostasis, nitric oxide metabolism, and cellular aging.

Conclusions:

  • This study provides a comprehensive proteomic profile of younger Fontan patients, extending prior targeted research.
  • Elevated CYB5R3 and altered ECM organization represent potential biomarkers for risk stratification and therapeutic intervention.
  • The findings highlight the intricate molecular complexity of the Fontan circulation, informing future clinical management and research.

Keywords:
CYB5R3Fontanbiomarkerscongenital heart diseasemass spectrometryproteomicsrisk stratificationsingle ventricle

More Related Videos

Low Molecular Weight Protein Enrichment on Mesoporous Silica Thin Films for Biomarker Discovery13:00

Low Molecular Weight Protein Enrichment on Mesoporous Silica Thin Films for Biomarker Discovery

Published on: April 17, 2012

14.0K
Skeletal Muscle Gender Dimorphism from Proteomics09:29

Skeletal Muscle Gender Dimorphism from Proteomics

Published on: December 14, 2011

13.0K

Related Concept Videos

Molecular Chaperones and Protein Folding03:00

Molecular Chaperones and Protein Folding

The native conformation of a protein is formed by interactions between the side chains of its constituent amino acids. When the amino acids cannot form these interactions, the protein cannot fold by itself and needs chaperones. Notably, chaperones do not relay any additional information required for the folding of polypeptides; the native conformation of a protein is determined solely by its amino acid sequence. Chaperones catalyze protein folding without being a part of the folded protein.
The...
19.9K
Molecular Chaperones and Protein Folding03:00

Molecular Chaperones and Protein Folding

15.1K
Key Elements for Plant Nutrition02:35

Key Elements for Plant Nutrition

Like all living organisms, plants require organic and inorganic nutrients to survive, reproduce, grow and maintain homeostasis. To identify nutrients that are essential for plant functioning, researchers have leveraged a technique called hydroponics. In hydroponic culture systems, plants are grown—without soil—in water-based solutions containing nutrients. At least 17 nutrients have been identified as essential elements required by plants. Plants acquire these elements from the...
24.4K
Key Techniques in Microbiology01:19

Key Techniques in Microbiology

Aseptic techniques prevent contamination, ensure experimental accuracy, and protect researchers and microbial cultures. These techniques are essential in clinical, industrial, and research settings where sterility is required.Maintaining Sterility in Laboratory PracticesScientists maintain sterility by sterilizing tools with heat or chemicals, disinfecting work surfaces, and handling cultures in controlled environments. Working near an open flame or within a laminar flow hood reduces the risk...
2.5K
Physiological Pharmacokinetic Models: Assumption with Protein Binding01:13

Physiological Pharmacokinetic Models: Assumption with Protein Binding

Physiological models with protein binding in pharmacokinetics offer a sophisticated approach to understanding drug disposition. These models consider drug-protein interactions, enabling them to effectively predict drug concentrations in different organs and tissues. This precision aids in accurate drug dosing, providing a significant advantage over conventional models. A key process within these models is equilibration, which ensures that drug concentrations achieve a steady state within the...
265
Proteomics01:33

Proteomics

A proteome is the entire set of proteins that a cell type produces. We can study proteomes using the knowledge of genomes because genes code for mRNAs, and the mRNAs encode proteins. Although mRNA analysis is a step in the right direction, not all mRNAs are translated into proteins.
Proteomics is the study of proteomes' function. It involves the large-scale systematic study of the proteome to denote the protein complement expressed by a genome. Scientist Mark Wilkins coined the term...
9.9K