Dataset Information

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

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.

SUBMITTER: Chouvarine P

PROVIDER: S-EPMC7994198 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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

Chouvarine Philippe P Photiadis Joachim J Cesnjevar Robert R Scheewe Jens J Bauer Ulrike M M UMM Pickardt Thomas T Kramer Hans-Heiner HH Dittrich Sven S Berger Felix F Hansmann Georg G

iScience 20210227 3

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 ...[more]

PMID: 33786422

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Project description:Right ventricular (RV) pressure overload has a vastly different clinical course in children with idiopathic pulmonary arterial hypertension (iPAH) than in children with pulmonary stenosis (PS). While RV function is well recognized as a key prognostic factor in iPAH, adverse ventricular-ventricular interactions and LV dysfunction are less well characterized and the pathophysiology is incompletely understood. We compared ventricular-ventricular interactions as hypothesized drivers of biventricular dysfunction in pediatric iPAH versus PS Eighteen iPAH, 16 PS patients and 18 age- and size-matched controls were retrospectively studied. Cardiac cycle events were measured by M-mode and Doppler echocardiography. Measurements were compared between groups using ANOVA with post hoc Dunnet's or ANCOVA including RV systolic pressure (RVSP; iPAH 96.8 ± 25.4 mmHg vs. PS 75.4 ± 18.9 mmHg; P = 0.011) as a covariate. RV-free wall thickening was prolonged in iPAH versus PS, extending beyond pulmonary valve closure (638 ± 76 msec vs. 562 ± 76 msec vs. 473 ± 59 msec controls). LV and RV isovolumetric relaxation were prolonged in iPAH (P < 0.001; LV 102.8 ± 24.1 msec vs. 63.1 ± 13.7 msec; RV 95 [61-165] vs. 28 [0-43]), associated with adverse septal kinetics; characterized by rightward displacement in early systole and leftward displacement in late RV systole (i.e., early LV diastole). Early LV diastolic filling was decreased in iPAH (73 ± 15.9 vs. PS 87.4 ± 14.4 vs. controls 95.8 ± 12.5 cm/sec; P = 0.004). Prolonged RVFW thickening, prolonged RVFW isovolumetric times, and profound septal dyskinesia are associated with interventricular mechanical discoordination and decreased early LV filling in pediatric iPAH much more than PS These adverse mechanics affect systolic and diastolic biventricular efficiency in iPAH and may form the basis for worse clinical outcomes. We used clinically derived data to study the pathophysiology of ventricular-ventricular interactions in right ventricular pressure overload, demonstrating distinct differences between pediatric pulmonary arterial hypertension (iPAH) and pulmonary stenosis (PS). Altered timing of right ventricular free wall contraction and profound septal dyskinesia are associated with interventricular mechanical discoordination and decreased early LV filling in iPAH much more than PS These adverse mechanics affect systolic and diastolic biventricular efficiency, independent of right ventricular systolic pressure.

Dataset Information

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

Publications

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

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