Human Adult and Pediatric Multimodal Transcriptomic Atlas of Progression from Pressure-Loaded to Failing Right Ventricle [Xenium spatial transcriptomics]
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE345643 | GEO | 2026/09/04
REPOSITORIES: GEO
Similar Datasets
Project description:Single-nucleus RNA-sequencing of transmural right ventricular (RV) tissue from adult non-failing organ donors and transplant recipients with left ventricular failure, the latter stratified by RV function into pressure-loaded but preserved (pRV) and failing (RVF). Part of a multimodal atlas spanning bulk RNA-seq, snRNA-seq and Xenium spatial transcriptomics of the human RV.
2026-09-04 | GSE345646 | GEO
Project description:Bulk RNA-sequencing of right ventricular free-wall tissue from 142 human hearts spanning non-failing (NF, n=29), compensated/pressure-loaded right ventricle (pRV, n=78) and right ventricular failure (RVF, n=35). Part of an integrated atlas that also includes single-nucleus RNA-seq and Xenium spatial profiling of the same cohort.
2026-09-04 | GSE345645 | GEO
Project description:Right ventricular failure (RVF) due to pressure load is a major cause of death in congenital heart diseases and pulmonary hypertension. The mechanisms of RVF are yet unknown. Research is hampered by the lack of a good RVF model. Our aim was to study the pathophysiology of RVF in a rat model of chronic pressure load. Wistar rats (n=19) were subjected to pulmonary artery banding (PAB, 1.1mm) or sham surgery (CON). All PAB rats developed RVF (reduced cardiac output, RV stroke volume, TAPSE, increased end diastolic pressure, all p<0.05 vs. CON) but clinical symptoms of RVF (inactivity, ruffled fur, dyspnea, ascites) necessitating termination ensued in a subset (5/12) of rats (RVF+) after a period of 52±5 days. Rats with RVF+ had significantly worse RV function and pericardial effusion and liver congestion compared to RVF rats without symptoms (all p<0.05), despite similar pressure load (p=NS RVF vs. RVF+). Chronic pulmonary artery banding invariably leads to RV failure in rats, and a subset transitions to advanced clinical RVF. RVF is characterized by enhanced contractility, progressive diastolic dysfunction and derangement of energy metabolism, thus improving diastolic function and targeting RV metabolism may be the keys to treating RVF. Total RNA optainded ( Heart) of 7 Controls ,5 RVF+ and 4 RVF samples where used for this array study
2014-12-08 | E-GEOD-46863 | biostudies-arrayexpress
Project description:Right ventricular failure (RVF) due to pressure load is a major cause of death in congenital heart diseases and pulmonary hypertension. The mechanisms of RVF are yet unknown. Research is hampered by the lack of a good RVF model. Our aim was to study the pathophysiology of RVF in a rat model of chronic pressure load. Wistar rats (n=19) were subjected to pulmonary artery banding (PAB, 1.1mm) or sham surgery (CON). All PAB rats developed RVF (reduced cardiac output, RV stroke volume, TAPSE, increased end diastolic pressure, all p<0.05 vs. CON) but clinical symptoms of RVF (inactivity, ruffled fur, dyspnea, ascites) necessitating termination ensued in a subset (5/12) of rats (RVF+) after a period of 52±5 days. Rats with RVF+ had significantly worse RV function and pericardial effusion and liver congestion compared to RVF rats without symptoms (all p<0.05), despite similar pressure load (p=NS RVF vs. RVF+). Chronic pulmonary artery banding invariably leads to RV failure in rats, and a subset transitions to advanced clinical RVF. RVF is characterized by enhanced contractility, progressive diastolic dysfunction and derangement of energy metabolism, thus improving diastolic function and targeting RV metabolism may be the keys to treating RVF.
2014-12-08 | GSE46863 | GEO
Project description:Right ventricular heart failure (RVF) associated with pulmonary hypertension (PH) is characterized by a distinct gene expression pattern when compared with functional compensatory hypertrophy. Carvedilol treatment after RVF has been established reduces right ventricle (RV) hypertrophy and improves the RV function. In addition, carvedilol treatment has been shown to alter the gene expression of select genes. We sought to identify, on a genome-wide basis, the effect of carvedilol on gene expression. RVF was induced in male Sprague-Dawley rats by the combination of VEGF-receptor blockade and chronic hypoxia; thereafter, one group was treated with carvedilol. RNA was isolated from the RV and subjected to microarray analysis. A prediction analysis of the carvedilol-treated RVs showed that carvedilol treated RVs most resembled in their expression pattern the RVF pattern. However, an analysis beyond the boundaries of the prediction set revealed a small set of genes associated with carvedilol reversal of RVF. Pathway analysis of this set of genes revealed expression changes of genes involved in cardiac hypertrophy, mitochondrial dysfunction, protein ubiquitination, and sphingolipid metabolism. Genes encoding proteins in the cardiac hypertrophy and protein ubiquitination pathways were downregulated in the RV by carvedilol, while genes encoding proteins in the mitochondrial dysfunction and sphingolipid metabolism pathways were upregulated by carvedilol.
2013-05-06 | GSE42579 | GEO
Project description:Mechanical unloading by ventricular assist devices (VAD) leads to significant gene-expression changes often summarized as reverse remodeling. However, little is known on individual transcriptome changes during VAD-support and its relationship to non-failing hearts (NF). In addition no data are available for the transcriptome regulation during non-pulsatile VAD-support. Therefore we analysed the gene-expression patterns of 30 paired samples from VAD-supported (including 8 non-pulsatile VADs) and 8 non-failing control hearts (NF) using the first total human genome-array available. Transmural myocardial samples were collected for RNA-isolation. RNA was isolated by commercial methods and processed according to chip-manufacturer recommendations. cRNA were hybridized on Affymetrix HG-U133 Plus 2.0 arrays, providing coverage of the whole human genome Array. Data was analyzed using Microarray Analysis Suite 5.0 (Affymetrix) and clustered by Expressionist software (Genedata). 352 transcripts were differentially regulated between samples from VAD-implantation and NF, whereas 510 were significantly regulated between VAD-transplantation and NF (paired t-test p<0.001, fold change >=1.6). Remarkably, only a minor fraction of 111 transcripts was regulated in heart failure (HF) and during VAD-support. Unsupervised hierarchical clustering of paired VAD- and NF-samples revealed separation of HF- and NF- samples, however individual differentiation of VAD-implantation and VAD-transplantation was not accomplished. Clustering of pulsatile and non-pulsatile VAD did not lead to robust separation of gene expression patterns. During VAD-support myocardial gene expression changes do not indicate reversal of the HF-phenotype, but reveal a distinct HF-related pattern. Transcriptome analysis of pulsatile and non-pulsatile VAD-supported hearts did not provide evidence for a pump-mode specific transcriptome pattern. Microarrays were used to elucidate the differences between non-failing control hearts and those, suffering from end-stage heart failure pre and post mechanical unloading.
2010-07-29 | E-GEOD-21610 | biostudies-arrayexpress
Project description:Right ventricular dysfunction (RVD) independently predicts worse outcomes in both heart failure (HF) and pulmonary hypertension (PH), irrespective of their etiologies. Yet no evidence-based therapies exist for RVD and progression towards RV failure (RVF) can occur in spite of optimal medical treatment of HF or PH. This disparity reflects our insufficient understanding of the molecular pathophysiology of RVF. To identify molecular mechanisms that may uniquely underlie RVF, we investigated the cardiac ventricular transcriptome of advanced HF patients, with and without RVF. Using weighted gene co-expression network and module-phenotype analyses, we identified a 279-member gene module that correlated significantly and specifically with RVF. Within this module, WIPI1 served as a genetic hub, HSPB6, SNAP47, and MAP4 as drivers, and PRDX5 as a repressor of RVF. We subsequently confirmed the ventricular specificity and temporal relationship of Wipi1, Hspb6, and Map4 transcript expression changes in murine models of pressure overload induced RV failure versus LV failure and subsequently uncovered differential dysregulation of autophagy in the failing RV versus the failing LV, namely a shift towards excessive non-canonical, Beclin1-independent, Wipi1/LC3II-mediated autophagy in RVF. In vitro siRNA silencing of Wipi1 partially protected isolated neonatal rat ventricular cardiac myocytes against aldosterone-induced failing phenotype. Moreover, silencing Wipi1 blunted mitochondrial superoxide production and limited non-canonical autophagy in this in vitro RVF model. Our findings suggest that Wipi1 regulates mitochondrial oxidative signaling and autophagy in cardiac myocytes. Inhibition of Wipi1 may hold promise as a therapeutic target for RVF.
2018-10-05 | GSE120852 | GEO
Project description:A goal of this study was to identify and investigate previously unrecognized components of the remodeling process in the progression to heart failure by comparing gene expression in ischemic, failing (F) to non-failing (NF) hearts. These results also were compared to the changes observed in a proteomic analysis of F and NF hearts. RNA extracted from the left ventricle was hybridized to Affymetrix arrays to identify gene expression differences in ischemic, end-stage failing versus non-failing hearts. biological replicate: LV_NF_001, LV_NF002, LV_NF004, LV_NF005 biological replicate: LV_F_003, LV_F005, LV_F009, LV_F006
2016-02-08 | E-GEOD-76701 | biostudies-arrayexpress
Project description:Mechanical unloading by ventricular assist devices (VAD) leads to significant gene-expression changes often summarized as reverse remodeling. However, little is known on individual transcriptome changes during VAD-support and its relationship to non-failing hearts (NF). In addition no data are available for the transcriptome regulation during non-pulsatile VAD-support. Therefore we analysed the gene-expression patterns of 30 paired samples from VAD-supported (including 8 non-pulsatile VADs) and 8 non-failing control hearts (NF) using the first total human genome-array available. Transmural myocardial samples were collected for RNA-isolation. RNA was isolated by commercial methods and processed according to chip-manufacturer recommendations. cRNA were hybridized on Affymetrix HG-U133 Plus 2.0 arrays, providing coverage of the whole human genome Array. Data was analyzed using Microarray Analysis Suite 5.0 (Affymetrix) and clustered by Expressionist software (Genedata). 352 transcripts were differentially regulated between samples from VAD-implantation and NF, whereas 510 were significantly regulated between VAD-transplantation and NF (paired t-test p<0.001, fold change >=1.6). Remarkably, only a minor fraction of 111 transcripts was regulated in heart failure (HF) and during VAD-support. Unsupervised hierarchical clustering of paired VAD- and NF-samples revealed separation of HF- and NF- samples, however individual differentiation of VAD-implantation and VAD-transplantation was not accomplished. Clustering of pulsatile and non-pulsatile VAD did not lead to robust separation of gene expression patterns. During VAD-support myocardial gene expression changes do not indicate reversal of the HF-phenotype, but reveal a distinct HF-related pattern. Transcriptome analysis of pulsatile and non-pulsatile VAD-supported hearts did not provide evidence for a pump-mode specific transcriptome pattern.
2010-05-20 | GSE21610 | GEO
Project description:A goal of this study was to identify and investigate previously unrecognized components of the remodeling process in the progression to heart failure by comparing gene expression in ischemic, failing (F) to non-failing (NF) hearts. These results also were compared to the changes observed in a proteomic analysis of F and NF hearts.
2016-02-08 | GSE76701 | GEO