Human Adult and Pediatric Multimodal Transcriptomic Atlas of Progression from Pressure-Loaded to Failing Right Ventricle [murine pulmonary artery banding single-nucleus RNA-seq]
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE345854 | GEO | 2026/09/04
REPOSITORIES: GEO
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Project description:Xenium in situ spatial transcriptomics of transmural right ventricular (RV) sections from adult human hearts spanning non-failing donors (NF), pressure-loaded but functionally preserved RVs (pRV), and failing RVs (RVF). Nine sections (one per patient, 3 per group; 625,305 cells) were profiled with a 477-gene panel. Part of a multimodal atlas that also includes bulk RNA-seq, single-nucleus RNA-seq and a murine pulmonary artery banding model.
2026-09-04 | GSE345643 | GEO
Project description:Background: Right ventricular(RV) function determines outcomes in RV pressure-loading. A better understanding of the time-course and regional distribution of RV remodeling may help optimize targets and timing for therapeutic intervention. We sought to characterize RV remodeling between zero and 6-weeks after initiation of RV pressure-loading. Methods and results: Thirty-six rats were randomized to either sham surgery or to pulmonary artery banding(PAB). After echocardiography and conductance catheter studies, groups of rats were euthanized at 1-week, 3-weeks, and 6-weeks after sham surgery, or induction of RV pressure-loading, for RV histological, RNA and molecular analysis. A vigorous inflammatory response characterized by increased RV inflammatory cytokines, chemokines and macrophage markers was observed at 1-week following PAB. Metabolic changes, TGF-β1 canonical signaling, collagenous fibrosis deposition and apoptosis were already significantly increased by 1-week after PAB. Genes marking fibroblast activation were upregulated at 1-week but not 6-week post-PAB surgery. Mitochondrial dysfunction as evidenced by increased PDK activity and decreased PDH phosphorylation significantly at 6-week post PAB. These processes preceded the development of overt myocardial hypertrophy and impaired echo parameters of systolic and diastolic function which occurred significantly from 3-weeks after PAB. Conclusion: RV myocardial inflammation, metabolic shift, metabolic gene transcription and pro-fibrotic signaling occur early after initiation of pressure-loading when RV pressures are only moderately elevated, before the development of overt myocardial hypertrophy and dysfunction, suggesting that adaptive hypertrophy and maladaptive remodeling occur simultaneously. These results suggest that therapeutic intervention to reduce adverse RV remodeling may be needed earlier and at lower thresholds than currently employed
2025-12-31 | GSE272615 | GEO
Project description:Background: Right ventricular (RV) and left ventricular (LV) myocardium differ in their response to pressure-overload hypertrophy (POH). In this report we use microarray and proteomic analyses to identify pathways modulated by LV-, and RV-POH in the immature heart. Methods: Newborn New Zealand White rabbits underwent banding of the descending thoracic aorta (LV-POH; n=6). RV-POH was achieved by banding the pulmonary artery (n=6). Sham–control animals (SC; n=6 each) were sham-manipulated. Following 4 (LV-POH) and 6 weeks (RV-POH) recovery, the hearts were removed and matched sample RNA and proteins were isolated for microarray and proteomic analysis. Results: There was no difference in body weight in RV-, LV-POH vs. SC but there was a significant increase vs. SC in RV (3.2±0.8g vs. 1.2±0.3g; P<0.01) and LV weight (7.08±0.6g vs. 4.02±0.2g; P<0.01). Fractional area change (RV-POH) and shortening fraction (LV-POH) decreased significantly (23±6 vs. 47±6 and 21±4 vs.44±2, respectively, P<0.01). Microarray analysis demonstrated that LV-POH enriched pathways for oxidative phosphorylation, mitochondria energy pathways, actin, ILK, hypoxia, calcium and protein kinase-A signalling. RV-POH enriched pathways for cardiac oxidative phosphorylation. Proteomic analysis revealed 19 proteins were uniquely expressed in LV-POH vs. SC. Functional annotation clustering analysis indicated significant enrichment for the mitochondrion, cellular macromolecular complex assembly and oxidative phosphorylation. RV-POH had 15 uniquely expressed proteins vs. SC. Functional annotation clustering analysis indicated significant enrichment in structural constituents of muscle, cardiac muscle tissue development and calcium handling. Conclusion: Our results identify unique transcript and protein expression profiles in LV, RV-POH and provide new insight into the biological basis of ventricular specific hypertrophy. 3 different conditions: PAB-RV vs. Sham-control RV, PAB-RV [test] vs. PAB-LV [control], AOB-LV vs. Sham-control LV.
2011-06-24 | E-GEOD-30194 | biostudies-arrayexpress
Project description:Disease animal models play an extremely important role in preclinical research. Lack of corresponding animal models, many basic research cannot be carried out, and the conclusions obtained are incomplete or even incorrect. Right ventricular (RV) outflow tract (RVOT) obstruction leads to RV pressure overload (PO) and reduced pulmonary blood flow (RPF), which are two of the most important pathophysiological characteristics in pediatric cardiovascular diseases, and seriously affect the survival rate and long-term life quality of many children. Due to the lack of a neonatal mouse model for RVOT obstruction, it is largely unknown how RV PO and RPF regulate postnatal RV and pulmonary development. Thus, many treatment are directly applied from adults despite significant differences in cardiovascular physiology between infants and adults, with limited or even harmful results. Here we firstly introduced a neonatal mouse model of RVOT obstruction by pulmonary artery banding (PAB) on postnatal day 1. PAB induced neonatal RVOT obstruction, RV PO, and RPF. Neonatal RV PO induced cardiomyocyte proliferation, and neonatal RPF induced pulmonary dysplasia, the two features that can not be observed in adult RVOT obstruction. As a result, PAB pups exhibited overall developmental dysplasia, a sign similar to that of children with RVOT obstruction. Since many pediatric cardiovascular diseases are associated with RV PO and RPF, the introduction of neonatal mouse model of RVOT obstruction may greatly enhance our understanding of those diseases, and eventually save or improve the lives of many children. We used C57 mice in this study and divided them into sham and PAB group, each group contain 3 replicates.
2024-05-09 | GSE232054 | GEO
Project description:To investigate the effect of pressure overload (PO) during postnatal right ventricular (RV) development, we established the RV PO model by conducting pulmonary artery banding (PAB) surgery on neonatal Sprague-Dawley (SD) rats. We then performed gene expression and chromatin openness profiling analysis using data obtained from RNA-seq and ATAC-seq of RV free walls from PO and sham-operated rats at postnatal day 21 (P21).
2024-05-17 | GSE210180 | GEO
Project description:Background: Current mammalian model for heart regeneration research is limited in apex amputation or myocardium infarction, both of which are controversy. Moreover, RNAseq demonstrated there were a very limited set of differential expressed genes between sham and operation heart in the myocardium infarction model. Here we investigated whether pressure overload in the right ventricle(RV), a common phenomenon in congenital heart disease children, could be a better animal model for heart regeneration study when consider cardiomyocyte(CM) proliferation as the most important index. Methods and results: Pressure overload was induced by pulmonary artery banding (PAB) on day1 and confirmed by echocardiography and hemodynamic measurements at postnatal day 7(P7). RNAseq analyses of purified RVCM at P7 from PAB and sham-operated rats revealed there were 5469 differential expressed genes between these two groups. GO and KEGG analysis showed that these genes mainly mediated mitosis and cell division. Cell proliferation assay indicates a continuous over-proliferation of RVCM after PAB, in particular for P3. In addition, there were ~2 times-fold increase of Ki67/Phh3 -positive CM in human overload RV compared to non-overload RV. Other features about this model included CM hypotrophy and no fibrosis.. Conclusions: Pressure overload profoundly promotes RVCM proliferation in the neonatal stage both in rats and human beings, activated a regeneration-specific gene program, and may offer a better alternative animal model for heart regeneration research..
2020-08-19 | GSE139561 | GEO
Project description:Purpose: While women are more susceptible to pulmonary arterial hypertension (PAH) than men, their right ventricular (RV) function is better preserved. Experimental studies have identified estrogen receptor alpha (ERα) as a likely mediator for estrogen protection in the RV. However, the role of ERα in preserving RV function and remodeling during pressure overload remains poorly understood. We hypothesized that loss of functional ERα removes female protection from adverse remodeling and is permissive for development of a maladapted RV phenotype. Methods: Male and female rats with a loss-of-function mutation in ERα (ERαMut) and wildtype (WT) littermates, while at their surgical plane of anesthesia, underwent RV pressure overload by pulmonary artery banding (PAB) or a sham surgery. Results: At 10 weeks post-PAB, WT and ERαMut demonstrated RV hypertrophy. Single beat analysis and Tau Weiss calculation from RV pressure waveforms (collected during surgical plane of anesthesia) demonstrated uncoupling of the RV-pulmonary vascular circuit and diastolic dysfunction, respectively, in female, but not male, ERαMut PAB rats. Similarly, female, but not male, ERαMut exhibited increased RV fibrosis, comprised primarily of stiffer collagen type I, suggesting RV stiffening by collagen type I accumulation. RNA-sequencing in female WT and ERαMut RV revealed Kallikrein related-peptidase 10 (Klk10) and Jun Proto-Oncogene (Jun) as possible mediators of female RV protection during PAB. Conclusions: ERα in females is protective against RV-pulmonary vascular uncoupling, diastolic dysfunction, and fibrosis in response to pressure overload. ERα appears to be dispensable for RV adaptation in males. ERα may be a mediator of superior RV adaptation in female patients with PAH.
2020-04-11 | GSE148453 | GEO
Project description:We utilized an animal model of RV pressure overload created by banding the pulmonary artery (PAB). Two weeks post-banding, bone marrow-derived mesenchymal stromal cells (MSCs) and 3 populations of CPCs (nCPCs, cCPCs, ES-CPCs) were delivered to the RV free wall. RV function and cellular retention were measured for four weeks post-injection, at which point hearts were extracted and the RV was excised for liquid chromatography and tandem mass spectrometry. Resulting RV proteomes were compared and analyzed using systems biology and bioinformatics.
2024-10-17 | PXD051582 | Pride
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: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