Integrated transcriptomics and proteomics analysis reveal potential target in pediatric primary restrictive...

Area of Science:

• Cardiology
• Genomics
• Proteomics
• Molecular Biology

Background:

• Pediatric restrictive cardiomyopathy (RCM) has a complex etiology and limited treatment options.
• Understanding RCM's molecular mechanisms is crucial for identifying new therapeutic targets.

Purpose of the Study:

• To elucidate the molecular mechanisms of pediatric RCM.
• To identify potential therapeutic targets for RCM.

Main Methods:

• Integrated transcriptomic and proteomic analyses of myocardial tissues from RCM patients and controls.
• Differential gene and protein expression analysis using stringent statistical thresholds.
• Pathway enrichment analysis and validation studies (RT-PCR, Western blot).
• Bioinformatic prediction of therapeutic candidates.

Main Results:

• Identified 23 consistently dysregulated genes/proteins central to RCM pathogenesis.
• Confirmed significant expression changes in hub genes and marked downregulation of CKB, PGAM2, and TPM2 proteins.
• Highlighted involvement in muscle contraction, sarcomere organization, and extracellular matrix remodeling pathways.
• Predicted repurposed drugs including phenytoin, diazepam, and paricalcitol.

Conclusions:

• Elucidated molecular mechanisms of muscle contraction and energy metabolism in RCM.
• Identified downregulated proteins as potential biomarkers for RCM.
• Proposed drug repurposing strategies for RCM based on pathway analysis.
• Provided a foundation for developing targeted diagnostic and therapeutic tools for RCM.