Pathogenic Roles of Cardiac Fibroblasts in Pediatric Dilated Cardiomyopathy.

Area of Science:

• Cardiovascular Biology
• Cellular Physiology
• Genomics

Background:

• Dilated cardiomyopathy (DCM) is a leading cause of pediatric heart failure.
• Genetic causes remain unidentified in many DCM cases, suggesting non-cardiomyocyte involvement.
• The role of cardiac fibroblasts (CFs), the most abundant cardiac cells, in DCM is poorly understood.

Purpose of the Study:

• To investigate the pathological role of cardiac fibroblasts (CFs) in pediatric dilated cardiomyopathy (DCM).
• To compare gene expression and functional impact of DCM-derived CFs versus healthy CFs.

Main Methods:

• Primary cardiac fibroblast (CF) cell lines were cultured from pediatric DCM patients and healthy controls.
• Standard cell assays (proliferation, adhesion, migration, apoptosis) and atomic force microscopy were performed.
• Co-culture experiments with healthy cardiomyocytes and RNA sequencing were conducted.

Main Results:

• DCM CFs showed no significant differences in cellular behavior or physical properties compared to healthy CFs.
• Co-culture with DCM CFs impaired the contractile and diastolic functions of healthy cardiomyocytes.
• RNA sequencing revealed distinct gene expression profiles in DCM CFs, affecting pathways like ECM receptor interactions and TGF-β signaling.

Conclusions:

• Cardiac fibroblasts (CFs) from DCM patients do not exhibit altered intrinsic cellular properties.
• DCM CFs negatively impact cardiomyocyte function via humoral factors and direct cell contact.
• These findings implicate CFs as key contributors to DCM pathogenesis.