Volume Overload Initiates an Immune Response in the Right Ventricle at the Neonatal Stage

Area of Science:

• Cardiovascular Research
• Pediatric Cardiology
• Immunology

Background:

• Pediatric tetralogy of Fallot (TOF) surgical correction can cause pulmonary regurgitation, leading to chronic right ventricular (RV) volume overload (VO) and adolescent RV dysfunction.
• Understanding the molecular mechanisms of neonatal RV remodeling due to VO is crucial for improving post-surgical management of pediatric TOF.

Purpose of the Study:

• To establish a neonatal cardiac VO rat model to investigate the early molecular changes in the RV.
• To explore the role of immune responses in neonatal RV remodeling induced by VO.

Main Methods:

• A fistula was created between the abdominal aorta and inferior vena cava in P1 rats to induce neonatal VO.
• Echocardiography was used to assess pulmonary artery parameters.
• RV tissue was analyzed using RNA-sequencing (RNA-seq) and flow cytometry.

Main Results:

• Neonatal VO induced significant increases in pulmonary artery velocity and velocity-time integral, along with RV dilation.
• RNA-seq analysis revealed enrichment of immune response pathways (GO and KEGG) in the neonatal RV.
• Flow cytometry showed a significant increase in CD4+ and CD8+ immune cells in VO rats.

Conclusions:

• A successful neonatal cardiac VO rat model was developed for studying RV remodeling.
• Neonatal VO triggers an immune response, indicating that immune activation may initiate RV remodeling.
• Immunosuppressive therapies could potentially prevent VO-induced RV remodeling in pediatric TOF patients.