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

Autor:	Pollmann K; Department of Congenital Heart Defects and Pediatric Cardiology, German Heart Center Munich, Technical University of Munich, Munich, Germany., Raj Murthi S; Department of Congenital Heart Defects and Pediatric Cardiology, German Heart Center Munich, Technical University of Munich, Munich, Germany., Kračun D; Department of Congenital Heart Defects and Pediatric Cardiology, German Heart Center Munich, Technical University of Munich, Munich, Germany.; Experimental and Molecular Pediatric Cardiology, Department of Congenital Heart Defects and Pediatric Cardiology, German Heart Center Munich, Technical University of Munich, Munich, Germany., Schwarzmayr T; Institute of Human Genetics, Helmholtz Centrum Munich, German Research Center for Environmental Health, Neuherberg, Germany., Petry A; Department of Congenital Heart Defects and Pediatric Cardiology, German Heart Center Munich, Technical University of Munich, Munich, Germany.; Experimental and Molecular Pediatric Cardiology, Department of Congenital Heart Defects and Pediatric Cardiology, German Heart Center Munich, Technical University of Munich, Munich, Germany., Cleuziou J; Department of Congenital and Pediatric Heart Surgery, German Heart Center Munich, Technical University of Munich, Munich, Germany.; INSURE (Institute for Translational Cardiac Surgery), Department of Cardiovascular Surgery, German Heart Center Munich, Technical University of Munich, Munich, Germany., Hörer J; Department of Congenital and Pediatric Heart Surgery, German Heart Center Munich, Technical University of Munich, Munich, Germany., Klop M; Department of Congenital Heart Defects and Pediatric Cardiology, German Heart Center Munich, Technical University of Munich, Munich, Germany.; Experimental and Molecular Pediatric Cardiology, Department of Congenital Heart Defects and Pediatric Cardiology, German Heart Center Munich, Technical University of Munich, Munich, Germany., Ewert P; Department of Congenital Heart Defects and Pediatric Cardiology, German Heart Center Munich, Technical University of Munich, Munich, Germany.; DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany., Görlach A; Department of Congenital Heart Defects and Pediatric Cardiology, German Heart Center Munich, Technical University of Munich, Munich, Germany.; Experimental and Molecular Pediatric Cardiology, Department of Congenital Heart Defects and Pediatric Cardiology, German Heart Center Munich, Technical University of Munich, Munich, Germany.; DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany., Wolf CM; Department of Congenital Heart Defects and Pediatric Cardiology, German Heart Center Munich, Technical University of Munich, Munich, Germany.; DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany.
Jazyk:	angličtina
Zdroj:	Cardiovascular diagnosis and therapy [Cardiovasc Diagn Ther] 2021 Dec; Vol. 11 (6), pp. 1295-1309.
DOI:	10.21037/cdt-20-894
Abstrakt:	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. Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/cdt-20-894). The series “Current Management Aspects in Adult Congenital Heart Disease (ACHD): Part IV” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare. (2021 Cardiovascular Diagnosis and Therapy. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu