Connecting transcriptomics with computational modeling to reveal developmental adaptations in pediatric human atrial...

Area of Science:

• Cardiovascular Biology
• Pediatric Cardiology
• Molecular Cardiology

Background:

• Congenital heart disease affects nearly 1% of newborns, often necessitating early-life surgery.
• Understanding cardiomyocyte maturation is crucial for managing pediatric cardiac diseases and guiding treatment decisions.
• Limited knowledge exists regarding temporal changes in cardiomyocytes during postnatal development.

Purpose of the Study:

• To investigate age-dependent adaptations in cardiac gene expression and electrophysiology in pediatric patients.
• To identify molecular mechanisms underlying human cardiac maturation from infancy to adolescence.
• To correlate gene expression changes with electrophysiological properties like action potential and calcium transients.

Main Methods:

• Analysis of right atrial tissue samples from 117 pediatric patients stratified into five age groups.
• Measurement of age-dependent cardiac gene expression using transcriptomics.
• Computational modeling to simulate action potential and calcium transients based on gene expression data.

Main Results:

• Identified age-dependent changes in biological processes, including cell cycle and structural organization.
• Observed age-related trends in cardiac ion channel and calcium handling gene expression.
• Linked changes in calcium handling (I_NCX) and repolarization (I_K1) to action potential alterations.
• Noted lower I_Kr expression in younger patients, potentially compensated by increased I_Ks.

Conclusions:

• This study provides critical insights into the molecular basis of human cardiac maturation.
• Age-dependent shifts in gene expression and electrophysiology are key to understanding pediatric heart development.
• Findings can inform clinical strategies for surgical repair and postoperative care in congenital heart disease patients.