RNA expression profiles and regulatory networks in human right ventricular hypertrophy due to high pressure load
Philippe Chouvarine,
Joachim Photiadis,
Robert Cesnjevar,
Jens Scheewe,
Ulrike M.M. Bauer,
Thomas Pickardt,
Hans-Heiner Kramer,
Sven Dittrich,
Felix Berger,
Georg Hansmann
Affiliations
Philippe Chouvarine
Department of Pediatric Cardiology and Critical Care, Hannover Medical School, Hannover, Germany
Joachim Photiadis
Departments of Pediatric Cardiology and Pediatric Cardiac Surgery, German Heart Institute, German Center for Cardiovascular Research (DZHK) partner site Berlin, Berlin, Germany; Competence Network for Congenital Heart Defects (CNCHD), Berlin, Germany
Robert Cesnjevar
Departments of Pediatric Cardiology and Pediatric Cardiac Surgery, Friedrich-Alexander University of Erlangen-Nürnberg, Erlangen, Germany; Competence Network for Congenital Heart Defects (CNCHD), Berlin, Germany
Jens Scheewe
Divisions of Pediatric Cardiology and Pediatric Cardiac Surgery, Heart Center, University of Kiel, German Center for Cardiovascular Research (DZHK) partner site Hamburg/Kiel/Lübeck, Kiel, Germany; Competence Network for Congenital Heart Defects (CNCHD), Berlin, Germany
Ulrike M.M. Bauer
Competence Network for Congenital Heart Defects (CNCHD), Berlin, Germany; National Register for Congenital Heart Defects, German Center for Cardiovascular Research (DZHK), Berlin, Germany
Thomas Pickardt
Competence Network for Congenital Heart Defects (CNCHD), Berlin, Germany; National Register for Congenital Heart Defects, German Center for Cardiovascular Research (DZHK), Berlin, Germany
Hans-Heiner Kramer
Divisions of Pediatric Cardiology and Pediatric Cardiac Surgery, Heart Center, University of Kiel, German Center for Cardiovascular Research (DZHK) partner site Hamburg/Kiel/Lübeck, Kiel, Germany; Competence Network for Congenital Heart Defects (CNCHD), Berlin, Germany
Sven Dittrich
Departments of Pediatric Cardiology and Pediatric Cardiac Surgery, Friedrich-Alexander University of Erlangen-Nürnberg, Erlangen, Germany; Competence Network for Congenital Heart Defects (CNCHD), Berlin, Germany
Felix Berger
Departments of Pediatric Cardiology and Pediatric Cardiac Surgery, German Heart Institute, German Center for Cardiovascular Research (DZHK) partner site Berlin, Berlin, Germany; Competence Network for Congenital Heart Defects (CNCHD), Berlin, Germany
Georg Hansmann
Department of Pediatric Cardiology and Critical Care, Hannover Medical School, Hannover, Germany; Competence Network for Congenital Heart Defects (CNCHD), Berlin, Germany; Corresponding author
Summary: Right ventricular hypertrophy (RVH) occurs in high pressure afterload, e.g., tetralogy of Fallot/pulmonary stenosis (TOF/PS). Such RVH is associated with alterations in energy metabolism, neurohormonal and epigenetic dysregulation (e.g., microRNA), and fetal gene reprogramming in animal models. However, comprehensive expression profiling of competing endogenous RNA in human RVH has not been performed. Here, we unravel several previously unknown circular, long non-coding, and microRNAs, predicted to regulate expression of genes specific to human RVH in the non-failing heart (TOF/PS). These genes are significantly overrepresented in pathways related to regulation of glucose and lipid metabolism (SIK1, FABP4), cell surface interactions (THBS2, FN1), apoptosis (PIK3IP1, SIK1), extracellular matrix composition (CTGF, IGF1), and other biological events. This is the first unbiased RNA sequencing study of human compensated RVH encompassing coding and non-coding RNA expression and predicted sponging of miRNAs by non-coding RNAs. These findings advance our understanding of adaptive RVH and highlight future therapeutic targets.
