Molecular signaling pathways in right ventricular impairment of adult patients after tetralogy of Fallot repair.

Pollmann, Kathrin; Raj Murthi, Sarala; Kračun, Damir; Schwarzmayr, Thomas; Petry, Andreas; Cleuziou, Julie; Hörer, Jürgen; Klop, Mathieu; Ewert, Peter; Görlach, Agnes; Wolf, Cordula Maria

doi:10.21037/cdt-20-894

2021

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Titel:: Molecular signaling pathways in right ventricular impairment of adult patients after tetralogy of Fallot repair.
Dokumenttyp:: Article; Journal Article
Autor(en):: Pollmann, Kathrin; Raj Murthi, Sarala; Kračun, Damir; Schwarzmayr, Thomas; Petry, Andreas; Cleuziou, Julie; Hörer, Jürgen; Klop, Mathieu; Ewert, Peter; Görlach, Agnes; Wolf, Cordula Maria
Abstract:: BACKGROUND: Right ventricular impairment (RVI) secondary to altered hemodynamics contributes to morbidity and mortality in adult patients after tetralogy of Fallot (TOF) repair. The goal of this study was to describe signaling pathways contributing to right ventricular (RV) remodeling by analyzing over lifetime alterations of RV gene expression in affected patients. METHODS: RV tissue was collected at the time of cardiac surgery in 13 patients with a diagnosis of TOF. RNA was isolated and whole transcriptome sequencing was performed. Gene profiles were compared between a group of 6 adults with signs of RVI undergoing right ventricle to pulmonary artery conduit surgery and a group of 7 infants, undergoing TOF correction. Definition of RVI in adult patients was based on clinical symptoms, evidence of RV hypertrophy, dilation, dysfunction or elevated pressure on echocardiographic, cardiovascular magnetic resonance, or catheterization evaluation. RESULTS: Median age was 34 years in RVI patients and 5 months in infants. Based on P adjusted value <0.01, RNA sequencing of RV specimens identified a total of 3,010 differentially expressed genes in adult patients with TOF and RVI as compared to infant patients with TOF. Gene Ontology and Kyoto Encyclopedia of Genes databases highlighted pathways involved in cellular metabolism, cell-cell communication, cell cycling and cellular contractility to be dysregulated in adults with corrected TOF and chronic RVI. CONCLUSIONS: RV transcriptome profiling in adult patients with RVI after TOF repair allows identification of signaling pathways, contributing to pathologic RV remodeling and helps in the discovery of biomarkers for disease progression and of new therapeutic targets.
Zeitschriftentitel:: Cardiovasc Diagn Ther
Jahr:: 2021
Band / Volume:: 11
Heft / Issue:: 6
Seitenangaben Beitrag:: 1295-1309
Volltext / DOI:: doi:10.21037/cdt-20-894
PubMed:: http://view.ncbi.nlm.nih.gov/pubmed/35070799
Print-ISSN:: 2223-3652
TUM Einrichtung:: Klinik für Kinderkardiologie und angeborene Herzfehler (Prof. Hess)
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