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

doi:10.1016/j.isci.2021.102232

RNA expression profiles and regulatory networks in human right ventricular hypertrophy due to high pressure load

iScience. 2021 Feb 27;24(3):102232. doi: 10.1016/j.isci.2021.102232. eCollection 2021 Mar 19.

Authors

Philippe Chouvarine¹, Joachim Photiadis^{2

3}, Robert Cesnjevar^{4

3}, Jens Scheewe^{5

3}, Ulrike M M Bauer^{3

6}, Thomas Pickardt^{3

6}, Hans-Heiner Kramer^{5

3}, Sven Dittrich^{4

3}, Felix Berger^{2

3}, Georg Hansmann^{1

3}

Affiliations

¹ Department of Pediatric Cardiology and Critical Care, Hannover Medical School, Hannover, Germany.
² Departments of Pediatric Cardiology and Pediatric Cardiac Surgery, German Heart Institute, German Center for Cardiovascular Research (DZHK) partner site Berlin, Berlin, Germany.
³ Competence Network for Congenital Heart Defects (CNCHD), Berlin, Germany.
⁴ Departments of Pediatric Cardiology and Pediatric Cardiac Surgery, Friedrich-Alexander University of Erlangen-Nürnberg, Erlangen, Germany.
⁵ 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.
⁶ National Register for Congenital Heart Defects, German Center for Cardiovascular Research (DZHK), Berlin, Germany.

Abstract

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.

Keywords: Molecular Biology; Omics.