Dataset Information

Influence of the Soluble Guanylate Cyclase Stimulator Riociguat on Myocardial Left Ventricular Proteome and microRNA expression after Experimental Aortic Stenosis in Mice

ABSTRACT: We analyzed global proteomic adaptations during heart failure (HF) progression in a mouse model, suffering from left ventricular pressure overload due to transverse aortic constriction (TAC) and in response to riociguat (RIO) treatment, to gain deeper insights in beneficial effects due to sGC stimulation on cardiac remodeling and HF. TAC and sham animals were treated with either riociguat (RIO; 3 mg/kg/day) or vehicle (VEH; Transcutol®/Cremophor®/water: 10%/20%/70%) for five weeks, starting three weeks post-op when cardiac hypertrophy was established, resulting in four treatment groups ( n=5-6 per group). At the end of the study, hearts were dissected and proteomes of the left ventricles (LV) were analyzed by mass spectrometry (MS).

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Heart, Cardiac Muscle Of Left Ventricle

DISEASE(S): Heart Failure

SUBMITTER: Alexander Benkner

LAB HEAD: Elke Hammer

PROVIDER: PXD024156 | Pride | 2022-07-19

REPOSITORIES: Pride

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Project description:Accurate and comprehensive de novo transcriptome profiling in heart is a central issue to better understand cardiac physiology and diseases. Although significant progress has been made in genome-wide profiling for quantitative changes in cardiac gene expression, current knowledge offers limited insights to the total complexity in cardiac transcriptome at individual exon level. To develop more robust bioinformatic approaches to analyze high-throughput RNA sequencing (RNA-Seq) data, with the focus on the investigation of transcriptome complexity at individual exon and transcript levels. In addition to overall gene expression analysis, the methods developed in this study were used to analyze RNA-Seq data with respect to individual transcript isoforms, novel spliced exons, novel alternative terminal exons, novel transcript clusters (i.e., novel genes) and long non-coding RNA genes. We applied these approaches to RNA-Seq data obtained from mouse hearts following pressure-overload induced by trans-aortic constriction. Based on experimental validations, analyses of the features of the identified exons/transcripts, and expression analyses including previously published RNA-Seq data, we demonstrate that the methods are highly effective in detecting and quantifying individual exons and transcripts. Novel insights inferred from the examined aspects of the cardiac transcriptome open ways to further experimental investigations. Our work provided a comprehensive set of methods to analyze mouse cardiac transcriptome complexity at individual exon and transcript levels. Applications of the methods may infer important new insights to gene regulation in normal and disease hearts in terms of exon utilization and potential involvement of novel components of cardiac transcriptome. Left ventricular tissues were collected from C57BL/6 mice after 1 week (hypertrophy stage, HY) and 8 weeks post trans-aortic constriction (TAC) procedure (heart failure stage, HF), respectively, and their corresponding Sham controls (Sham-HY, Sham-HF). To conduct RNA-Seq analysis, total RNAs from six TAC and Sham-operated mice at the HY stage and four TAC and corresponding Sham mice at the HF stage were obtained.

Dataset Information

Influence of the Soluble Guanylate Cyclase Stimulator Riociguat on Myocardial Left Ventricular Proteome and microRNA expression after Experimental Aortic Stenosis in Mice

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