Kathrin Pollmann1, Sarala Raj Murthi1, Damir Kračun1,2, Thomas Schwarzmayr3, Andreas Petry1,2, Julie Cleuziou4,5, Jürgen Hörer4, Mathieu Klop1,2, Peter Ewert1,6, Agnes Görlach1,2,6, Cordula Maria Wolf1,6. 1. Department of Congenital Heart Defects and Pediatric Cardiology, German Heart Center Munich, Technical University of Munich, Munich, Germany. 2. Experimental and Molecular Pediatric Cardiology, Department of Congenital Heart Defects and Pediatric Cardiology, German Heart Center Munich, Technical University of Munich, Munich, Germany. 3. Institute of Human Genetics, Helmholtz Centrum Munich, German Research Center for Environmental Health, Neuherberg, Germany. 4. Department of Congenital and Pediatric Heart Surgery, German Heart Center Munich, Technical University of Munich, Munich, Germany. 5. INSURE (Institute for Translational Cardiac Surgery), Department of Cardiovascular Surgery, German Heart Center Munich, Technical University of Munich, Munich, Germany. 6. DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany.
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. 2021 Cardiovascular Diagnosis and Therapy. All rights reserved.
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. 2021 Cardiovascular Diagnosis and Therapy. All rights reserved.
Authors: Joost P G Sluijter; Vera Verhage; Janine C Deddens; Frederieke van den Akker; Pieter A Doevendans Journal: Cardiovasc Res Date: 2014-01-30 Impact factor: 10.787
Authors: Jordan L Williams; Omer Cavus; Emefah C Loccoh; Sara Adelman; John C Daugherty; Sakima A Smith; Benjamin Canan; Paul M L Janssen; Sara Koenig; Crystal F Kline; Peter J Mohler; Elisa A Bradley Journal: Life Sci Date: 2018-01-31 Impact factor: 5.037
Authors: E O Weinberg; C D Thienelt; S E Katz; J Bartunek; M Tajima; S Rohrbach; P S Douglas; B H Lorell Journal: J Am Coll Cardiol Date: 1999-07 Impact factor: 24.094
Authors: Daniel M DeLaughter; Alexander G Bick; Hiroko Wakimoto; David McKean; Joshua M Gorham; Irfan S Kathiriya; John T Hinson; Jason Homsy; Jesse Gray; William Pu; Benoit G Bruneau; J G Seidman; Christine E Seidman Journal: Dev Cell Date: 2016-11-10 Impact factor: 12.270
Authors: Dusan Bilbija; Fred Haugen; Julia Sagave; Anton Baysa; Nasser Bastani; Finn Olav Levy; Allan Sirsjö; Rune Blomhoff; Guro Valen Journal: PLoS One Date: 2012-09-28 Impact factor: 3.240
Authors: Anne Marie Valente; Kimberlee Gauvreau; Gabriele Egidy Assenza; Sonya V Babu-Narayan; Jenna Schreier; Michael A Gatzoulis; Maarten Groenink; Ryo Inuzuka; Philip J Kilner; Zeliha Koyak; Michael J Landzberg; Barbara Mulder; Andrew J Powell; Rachel Wald; Tal Geva Journal: Heart Date: 2013-10-31 Impact factor: 5.994
Authors: Andrew R Bond; Dominga Iacobazzi; Safa Abdul-Ghani; Mohammed Ghorbel; Kate Heesom; Mariangela Wilson; Christopher Gillett; Sarah J George; Massimo Caputo; Saadeh Suleiman; Robert M R Tulloh Journal: Open Heart Date: 2018-01-03