Effect of neonatal right ventricular pressure overload on gene expression and regions of open chromatin during postnatal heart development
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE210180 | GEO | 2024/05/17
REPOSITORIES: GEO
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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: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: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: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: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: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:We reported the RNAseq analyses of pulmonary vein tissues at the age of postnatal day 21 (P21) on SD rats with or without pulmonary vein stenosis. Pulmonary vein stenosis was induced by performing pulmonary vein banding surgery within 24 hours postnatally. RNAseq analyses of the pulmonary vein tissues was generated at P21 from 3 sham-operated rats and 3 pulmonary vein banding rats. The results revealed that there were 1124 differentially expressed genes between PAB and sham group at P7, among which 714 were upregulated and 410 were downregulated.
2024-07-10 | GSE267175 | GEO
Project description:We performed molecular phenotyping of adaptive to maladaptive RV hypertrophy remodeling, using transcriptome analysis of RV tissue obtained from PAB rats. This data along with other datasets linked within this study, provides a resource to comprehensively compare human RV remodeling to the animal RV dysfunction models (PAB) and led to the validation of state-specific biomarkers and potential therapeutic targets for RV dysfunction.
2023-09-29 | GSE242014 | 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:We demonstrated that, four weeks after the pulmonary artery banding (PAB) operation, rats could be divided into two groups: an F+ group in which the fibrotic area occupied more than 6.5% of the whole area of the heart tissues, and an F- group in which the fibrotic area occupied less than 6.5% of this area. We used microarrays to elucidate the fibrosis initiating master factor using heart samples obtained from PAB or sham-operated rats.
2019-12-10 | GSE141650 | GEO