Altered Inflammatory State and Mitochondrial Function Identified by Transcriptomics in Paediatric Congenital Heart
Francesca Bartoli-Leonard1,2, Amy G Harris1, Kelly Saunders2
1Bristol Medical School, Faculty of Health Sciences, University of Bristol, Bristol BS8 1UD, UK.
International Journal of Molecular Sciences
|July 13, 2024
Summary
Congenital heart disease (CHD) is linked to mitochondrial dysfunction and increased inflammatory T-cells in the right ventricle (RV). This study reveals key molecular pathways contributing to reduced RV function in pediatric patients before surgery.
Area of Science:
- Cardiology
- Molecular Biology
- Immunology
Background:
- Congenital heart disease (CHD) is the most common birth defect, often requiring surgical intervention.
- Right ventricle (RV) function is crucial for long-term cardiac health in CHD patients.
- Understanding RV dysfunction mechanisms is vital for improving patient outcomes.
Purpose of the Study:
- To elucidate divergent molecular profiles between CHD and control RV tissue.
- To identify mechanisms underlying reduced RV function in pediatric CHD.
- To explore potential new therapeutic targets for RV dysfunction.
Main Methods:
- Transcriptomic profiling of RV biopsies from pediatric CHD patients and controls.
- In-silico deconvolution and functional network analysis of gene expression data.
- Histological analysis with CD45 and CD8 staining.
Main Results:
- Increased expression of mitochondrial dysfunction genes (RPPH1, RMPR) and inflammatory markers (CD8a, LAGE3, CD49a, caspase-1) in CHD RV tissue.
- Gene-set enrichment revealed dysfunctional mitochondrial pathways, particularly oxidative phosphorylation.
- Histology confirmed increased cellularity and T-cell infiltration (CD8+) in CHD RV tissue, with reduced CD4+ T-cells.
Conclusions:
- Pediatric CHD patients exhibit dysfunctional mitochondrial pathways in RV tissue prior to surgery.
- An increased presence of inflammatory T-cells, specifically CD8+ T-cells, is associated with RV dysfunction in CHD.
- Findings highlight novel molecular targets for therapeutic intervention in congenital heart disease.
