Transcriptomic profiling of right ventricular remodeling in CTEPH pig model
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ABSTRACT:
ORGANISM(S): Sus scrofa
PROVIDER: GSE284258 | GEO | 2025/05/29
REPOSITORIES: GEO
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Project description:Transcriptomic profiling of right ventricular remodeling in CTEPH pig model
| PRJNA1198085 | ENA
Project description:The objective of this project is to identify relevant mechanisms associated to maladaptive right ventricular hypertrophy (RV) in pulmonary hypertension (PH), beyond pressure overload. For that, we analyzed plasma samples from PH pig models by high-throughput proteomics. Four different experimental models in 48 Yucatan pigs were developed: chronic postcapillary PH by pulmonary vein banding (M1); chronic PH by aorto-pulmonary shunting (M2); RV pressure overload by pulmonary artery banding, thus without PH (M3); and a sham procedure (M0). Animals were evaluated at months 1, and 8 after surgery with right heart catheterization, cardiac magnetic resonance (CMR), and blood sampling, and myocardial tissue was analyzed with histology and molecular biology. Unbiased proteomic and metabolomic analyses were performed and compared among experimental groups and related to the severity of PH and RV dysfunction through integrative interactome networking.
2025-01-20 | PXD041643 | Pride
Project description:Right ventricular failure (RVF) is a leading cause of morbidity and mortality in multiple cardiovascular diseases, but there are no approved RV-targeted treatments for RVF as therapeutic targets are not clearly defined. Contemporary transcriptomic/proteomic evaluations of RVF are predominately conducted in small animal studies, and data from large animal models are sparse. Moreover, a comparison of the molecular mediators of RVF across species is lacking. Here, we used transcriptomics and proteomics analyses to define the molecular pathways associated with cardiac MRI-derived values of RV hypertrophy, dilation, and dysfunction in pulmonary artery banded (PAB) piglets. Publicly available data from rat monocrotaline-induced RVF and pulmonary arterial hypertension patients with preserved or impaired RV function were used to compare the three species. Transcriptomic and proteomic analyses identified changes in multiple metabolic pathways in the RV of PAB pigs, and pathway alterations that were conserved between species. However, disruptions in fatty acid oxidation (FAO) and electron transport chain (ETC) proteins were different across species. FAO and ETC proteins and transcripts were mostly downregulated in rats, but were predominately upregulated in PAB pigs. When compared to humans, the pig PAB molecular signature was more similar to patients with RVF than rodents. These data suggest there are divergent molecular responses of RVF across species, and pigs more accurately recapitulate the metabolic molecular signature of human RVF.
2023-03-01 | GSE224428 | GEO
Project description:Right ventricular (RV) failure plays a critical role in any type of heart failure. However, there is no specific therapy developed for RV failure. To understand RV failure, we focused on the RV specific genes. Global gene expression analysis showed that alternative complement pathway-related genes including C3 and Cfd were significantly upregulated in right ventricle in murine heart. We generated the RV failure by right ventricle-specific pressure overload model mice, pulmonary artery constriction (PAC), which induces RV failure around 14 days. In C3 knockout (C3KO) mice, PAC-induced RV dysfunction and fibrosis were significantly attenuated. C3a is produced from C3 by C3 convertase complex including Cfd. Cfd knockout mice also attenuated PAC-induced RV failure. Moreover, C3a receptor (C3aR) antagonist dramatically improved PAC-induced RV dysfunction in wild type mice. Here we revealed the crucial role of C3-Cfd-C3a-C3aR axis in RV failure and highlight the potential therapeutic target for RV failure with no pharmacologic option.
2021-09-07 | GSE183504 | GEO
Project description:We reported the RNAseq analyses of right ventricualr free wall myocardium in neonatal volume overload (VO) SD rat. VO was induced by the fistula between abdominal aorta and inferior vena cava (AVF) within 24 hours postnatally (P1). RNAseq analyses of RV free wall at P7 from VO and sham-operated rat revealed that there were 454 differentially expressed genes between VO and sham group at P7. GO analysis showed that in the VO and sham comparison, the upregulated genes mainly mediated immune system response and the downregulated genes mainly mediated apoptotic process at P7. VO has no effect to neonatal right ventricular cardiomyocyte proliferation.
2021-12-08 | GSE180643 | 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:Right ventricular failure was induced thourgh pulmonary banding in 11 pigs. Right ventricular failure was defined as a SRVP >50 mmHg during two hours. After right ventricular failure was induced, half the pigs were treatmed with a Glenn-shunt combined with pulmonary banding for one hour, and the other half served as control group with pulmonary banding only. The aim was to study the change in global gene expression during right ventricular failure due to pulmonary banding, and the effect of volume unloading during pulmonary banding. 11 pigs. Samples at the following time periods: 1) Baseline 2) Right ventricular failure 3) Treatment with modified Glenn-shunt/Control. After Right ventricular failure, pigs were divided into two groups a) Treatment with modified Glenn-shunt or b) Control group
2013-06-11 | E-GEOD-47814 | biostudies-arrayexpress
Project description:We reported the RNAseq analyses of right ventricle (RV) and left ventricle (LV) in neonatal volume overload (VO) and sham-operated SD rat. VO was induced by the fistula between abdominal aorta and inferior vena cava (AVF) within 24 hours postnatally (P1). RNAseq analyses of RV and LV free wall of P7 from VO and sham-operated rat. It demonstrated that the 1806 differentially expressed genes (DEGs) between RV and LV at the neonatal stage were primarily enriched in GTPase mediating signal transduction, insulin signaling pathway and thyroid hormone signaling pathway. VO produced 3 more times DEGs in LV than RV . GO analysis of these DEGs demonstrated that in the top 150 enriched terms, the LV comparison and RV comparison shared 34 terms (22.7%) in common. These commonly enriched terms were primarily associated with GTPase mediating signal transduction. KEGG analysis of these DEGs demonstrated that in the top 30 enriched terms, the LV comparison and RV comparison shared 14 terms (46.7%) in common. And insulin signaling pathway and thyroid hormone signaling pathway are the top two enriched terms in common. Regarding the differently enriched GO terms, they were primarily associated with lipid metabolism and ion channel in RV and primarily associated nucleic acid metabolism in LV. The top two differently enriched KEGG terms were arrhythmogenic right ventricular cardiomyopathy (ARVC) and adipocytokine signaling pathway in RV while microRNAs in cancer and longevity regulating pathway in LV. These results were further confirmed by the determination of metabolites.
2022-12-15 | GSE186247 | GEO
Project description:Background: In complex congenital heart disease patients such as those with tetralogy of Fallot, the right ventricle (RV) is subject to pressure overload, leading to RV hypertrophy and eventually RV failure. The mechanisms that promote the transition from stable RV hypertrophy to RV failure are unknown. We evaluated the role of mitochondrial bioenergetics in the development of RV failure. Methods: We created a murine model of RV pressure overload by pulmonary artery banding and compared with sham-operated controls. Gene expression by RNA-sequencing, oxidative stress, mitochondrial respiration, dynamics, and structure were assessed in pressure overload-induced RV failure. Results: RV failure was characterized by decreased expression of electron transport chain genes and mitochondrial antioxidant genes (aldehyde dehydrogenase 2 and superoxide dismutase 2) and increased expression of oxidant stress markers (heme oxygenase, 4-hydroxynonenal). The activities of all electron transport chain complexes decreased with RV hypertrophy and further with RV failure (oxidative phosphorylation: sham 552.3±43.07 vs. RV hypertrophy 334.3±30.65 vs. RV failure 165.4±36.72 pmol/(sec*ml), p<0.0001). Mitochondrial fission protein DRP1 did not change, while MFF decreased and fusion protein OPA1 decreased. In contrast, transcription of electron transport chain genes increased in the left ventricle of RV failure. Conclusion: Pressure overload-induced RV failure is characterized by decreased transcription and activity of electron transport chain complexes and increased oxidative stress which are associated with decreased energy generation. An improved understanding of the complex processes of energy generation could aid in developing novel therapies to mitigate mitochondrial dysfunction and delay the onset of RV failure.
2021-03-18 | GSE152413 | GEO
Project description:We reported the RNAseq analyses of right ventricualr free wall myocardium in young volume overload (VO) C57/BL6 mice.VO was induced by the fistula between abdominal aorta and inferior vena cava (AVF) on postnatal day 7(P7). RNAseq analyses of RV free wall at P14 and P21from VO and sham-operated mice revealed that there were 981 differentially expressed genes between VO and sham group at P14, this number increased to 1907 at P21, there were 3012 differentially expressed genes between P21 and P14 sham group, and the number increased to 3470 at the presence of VO. GO analysis showed that in the VO and sham comparison, the upregulated genes mainly mediated mitosis and cell division and the downregulated genes mainly mediated heart contraction at P14, and the upregulated genes mainly mediated immune response, and downregulated genes mainly mediated cellular respiration at P21. As expected, in the normal RV development during preadolescence (from P14 to P21), upregulated genes mainly mediated oxidative phosphorylation and cellular respiration and the downregulated genes mainly mediated vasculogenesis. VO changed the RV development, the upregulated genes mainly mediated heart contraction and the down regulated genes mainly mediated vasculogenesis and cell cycle. KEGG pathway analysis revealed that cell cycle pathway was upregulated and cardiac muscle contraction and thyroid hormone signaling pathway were downregulated between VO and sham group at P14, phagosome pathway was upregulated and citrate cycle (TCA) cycle and thermogenesis were downregulated at P21 between VO and sham group. In the normal RV development, TCA cycle and cardiac muscle contraction pathway were upregulated while VO changed that to the upregulations of cardiomyopathy pathways and thyroid hormone signaling pathway. All the above changes were further confirmed by the functional tests.
2021-08-16 | GSE157396 | GEO