Intractable Rare Dis Res. 2025;14(1):29-35. (DOI: 10.5582/irdr.2024.01063)

Mitochondrial metabolic maturation in postnatal right ventricle restricted by volume overload

Cao J, Xiao YY, Hong HF, Chen ZZ, Qin WJ

Right ventricular volume overload (RVVO) is a common hemodynamic abnormality in patients with congenital heart disease (CHD) and frequently leads to pathological cardiac remodeling. Our previous research demonstrated that RVVO disrupts the metabolic maturation of cardiomyocytes. Mitochondrial metabolic maturation, a crucial process in postnatal cardiomyocyte development, remains poorly understood under RVVO conditions. In this study, an mouse RVVO model was established on postnatal day 7 by creating a fistula between the abdominal aorta and inferior vena cava, confirmed by abdominal ultrasound and echocardiography. Transcriptomic analyses revealed significant downregulation of genes linked to mitochondrial metabolic maturation. Transmission electron microscopy showed impaired mitochondrial structure and maturation markers, while Seahorse assays demonstrated a marked reduction in oxidative phosphorylation rates in RVVO cardiomyocytes. These findings collectively indicated that RVVO restricted mitochondrial metabolic maturation in the postnatal RV. Targeting mitochondrial metabolic maturation could offer a promising therapeutic strategy to mitigate RVVO-induced pathological remodeling.

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