Right ventricular dysfunction following surgical repair of tetralogy of Fallot: Molecular pathways and therapeutic prospects - 01/03/25
, Yabo Wang , Qi An , Yunfei Ling ⁎ Abstract |
Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease (CHD). Although surgical correction of TOF is possible, patients often face challenges related to right ventricle dysfunction (RVD) post-surgery, which can significantly impact their long-term survival. The causes of RVD in TOF patients are complex, involving both the unique structural characteristics of the TOF heart and damage resulting from surgical interventions. Residual anatomical issues following TOF repair are often unavoidable, placing the RV under stress and leading to the activation of multiple molecular pathways. This review comprehensively outlines the causes of RVD in patients after TOF surgery, particularly focusing the molecular pathways that contribute to RVD, including established signaling pathways as well as emerging pathways identified through transcriptomic analysis of RV myocardium in TOF patients. We also highlight the features of these molecular pathways concerning RVD, as well as the influence of gender disparities on these molecular pathways. By interpreting the causes and molecular mechanisms underlying RVD after TOF surgery, this review provides new insights for managing RVD in repaired TOF, potentially paving the way for targeted therapies aimed at improving long-term outcomes for those affected by RVD.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Molecular pathways that contribute to RVD include oxidative stress, energy metabolic remodeling, Ca2+ homeostasis dysregulation, RAAS overactivation and ECM remodeling. The residual anatomical problems after TOF repair place the RV under stress, leading us to propose that the molecular mechanisms underlying RVD begin with oxidative stress. The initial stress eventually causes a shift in energy metabolism, with glycolysis increasing and fatty acid beta-oxidation decreasing. This change in energy metabolism leads to a decrease in ATP production. Oxidative stress and metabolic remodeling cause dysregulation of Ca2+ homeostasis, resulting in decreased systolic force of RV. The activation of RAAS is initially a compensatory response to the decline in RV contractility. However, when residual anatomical problems remain unresolved, excessive activation of the RAAS exacerbates ECM remodeling in RV, further impairing RV function.
Molecular pathways that contribute to RVD include oxidative stress, energy metabolic remodeling, Ca2+ homeostasis dysregulation, RAAS overactivation and ECM remodeling. The residual anatomical problems after TOF repair place the RV under stress, leading us to propose that the molecular mechanisms underlying RVD begin with oxidative stress. The initial stress eventually causes a shift in energy metabolism, with glycolysis increasing and fatty acid beta-oxidation decreasing. This change in energy metabolism leads to a decrease in ATP production. Oxidative stress and metabolic remodeling cause dysregulation of Ca2+ homeostasis, resulting in decreased systolic force of RV. The activation of RAAS is initially a compensatory response to the decline in RV contractility. However, when residual anatomical problems remain unresolved, excessive activation of the RAAS exacerbates ECM remodeling in RV, further impairing RV function.Le texte complet de cet article est disponible en PDF.
Highlights |
• | Details key molecular pathways driving RVD after TOF surgery. |
• | Highlights the differences between RV and LV dysfunction. |
• | Reviews therapeutic prospects targeting RVD molecular mechanisms. |
• | Explores cardiac dopamine receptor and adrenergic signaling pathway in RVD after TOF repair. |
• | Highlights gender's impact on molecular pathways in RVD post-TOF repair. |
Keywords : Tetralogy of Fallot, Right ventricular dysfunction, Molecular pathways, Gender disparities, Therapeutic prospects
Plan
Vol 184
Article 117924- mars 2025 Retour au numéro
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