Similar Datasets
Project description:Molecular signature of cardiac remodeling associated with Polymerase Gamma mutation
| PRJNA820762 | ENA
Project description:Cardiac fibrosis is a key aspect of heart failure, leading to reduced ventricular compliance and impaired electrical conduction in the myocardium. Various pathophysiologic conditions can lead to fibrosis in the left ventricle (LV) and/or right ventricle (RV). Despite growing evidence to support the transcriptomic heterogeneity of cardiac fibroblasts (CFs) in healthy and diseased states, there have been no direct comparisons of CFs in the LV and RV. Given the distinct natures of the ventricles, we hypothesized that LV and RV-derived CFs would display baseline transcriptomic differences that influence their proliferation and differentiation following injury. Bulk RNA sequencing of CFs isolated from healthy left and right cardiac ventricles indicated that left ventricle-derived CFs may be further along the myofibroblast transdifferentiation trajectory than cells isolated from the right ventricle. Single-cell RNA-sequencing (scRNA-seq) analysis of the two populations confirmed that Postn+ CFs are more enriched in the LV, whereas Igfbp3+ CFs were enriched in the RV at baseline. Notably, following pressure overload injury, the LV developed a larger subpopulation of pro-fibrotic Thbs4+/Cthrc1+ injury-induced CFs, while the RV showed unique expansion of two less-well characterized subpopulations of CFs (Igfbp3+ and Inmt+). These findings demonstrate that LV and RV-derived CFs display baseline subpopulation differences that may dictate their diverging responses to pressure overload injury. Further study of these subpopulations will elucidate their role in the development of fibrosis and inform whether LV and RV fibrosis require distinct treatments.
2024-02-28 | GSE254914 | GEO
Project description:Cardiomyopathy (CM) is an intrinsic weakening of the myocardium with contractile dysfunction and congestive heart failure (CHF). CHF has been postulated to result from decreased mitochondrial energy production and oxidative stress. The effects of decreased mitochondrial oxygen consumption can also accelerate with aging, with the mitochondrial theory of aging forming the basis of this knowledge. We previously showed DNA methylation changes in human hearts with CM. This was associated with mitochondrial DNA depletion, being another molecular marker of CM. We examined the relationship between mitochondrial dysfunction and cardiac epigenetic DNA methylation changes in both young and old mice. We used genetically engineered C57Bl/6 mice transgenic for a cardiac-specific mutant of the mitochondrial polymerase (termed Y955C). Y955C mice undergo left ventricular hypertrophy (LVH) at a young age (~94 days old), and LVH decompensated to CHF at old age (~255 days old). In Y955C hearts, 95 differentially expressed genes were found, while 4,452 genes were differentially expressed in aged hearts. Moreover, cardiac DNA methylation patterns differed between Y955C (4,506 peaks with 68.5% hypomethylation) and aged hearts (73,286 peaks with 80.2% hypomethylated). Correlatively, of the 95 Y955C-dependent differentially expressed genes, 30 genes (31.6%) also displayed differential DNA methylation; in the 4,452 age dependent differentially expressed genes, 342 gene (7.7%) displayed associated DNA methylation changes. Both Y955C and aging demonstrated significant enrichment of CACGTG-associated E-box motifs in differentially methylated regions. Cardiac mitochondrial polymerase dysfunction alters nuclear DNA methylation. Furthermore, aging causes a robust change in cardiac DNA methylation that is partially associated with mitochondrial polymerase dysfunction. This study addresses how Y955C-mutated mitochondrial DNA polymerase g and aging affect cardiac (left ventricle) gene expression and epigenetic nuclear DNA methylation.
2016-05-06 | GSE72889 | GEO
Project description:Cardiomyopathy (CM) is an intrinsic weakening of the myocardium with contractile dysfunction and congestive heart failure (CHF). CHF has been postulated to result from decreased mitochondrial energy production and oxidative stress. The effects of decreased mitochondrial oxygen consumption can also accelerate with aging, with the mitochondrial theory of aging forming the basis of this knowledge. We previously showed DNA methylation changes in human hearts with CM. This was associated with mitochondrial DNA depletion, being another molecular marker of CM. We examined the relationship between mitochondrial dysfunction and cardiac epigenetic DNA methylation changes in both young and old mice. We used genetically engineered C57Bl/6 mice transgenic for a cardiac-specific mutant of the mitochondrial polymerase (termed Y955C). Y955C mice undergo left ventricular hypertrophy (LVH) at a young age (~94 days old), and LVH decompensated to CHF at old age (~255 days old). In Y955C hearts, 95 differentially expressed genes were found, while 4,452 genes were differentially expressed in aged hearts. Moreover, cardiac DNA methylation patterns differed between Y955C (4,506 peaks with 68.5% hypomethylation) and aged hearts (73,286 peaks with 80.2% hypomethylated). Correlatively, of the 95 Y955C-dependent differentially expressed genes, 30 genes (31.6%) also displayed differential DNA methylation; in the 4,452 age dependent differentially expressed genes, 342 gene (7.7%) displayed associated DNA methylation changes. Both Y955C and aging demonstrated significant enrichment of CACGTG-associated E-box motifs in differentially methylated regions. Cardiac mitochondrial polymerase dysfunction alters nuclear DNA methylation. Furthermore, aging causes a robust change in cardiac DNA methylation that is partially associated with mitochondrial polymerase dysfunction. This study addresses how Y955C-mutated mitochondrial DNA polymerase g and aging affect cardiac (left ventricle) gene expression and epigenetic nuclear DNA methylation.
2016-05-06 | GSE72888 | GEO
Project description:Cardiac fibrosis is a key aspect of heart failure, leading to reduced ventricular compliance and impaired electrical conduction in the myocardium. Various pathophysiologic conditions can lead to fibrosis in the left ventricle (LV) and/or right ventricle (RV). Despite growing evidence to support the transcriptomic heterogeneity of cardiac fibroblasts (CFs) in healthy and diseased states, there have been no direct comparisons of CFs in the LV and RV. Given the distinct natures of the ventricles, we hypothesized that LV and RV-derived CFs would display baseline transcriptomic differences that influence their proliferation and differentiation following injury. Bulk RNA sequencing of CFs isolated from healthy left and right cardiac ventricles indicated that left ventricle-derived CFs may be further along the myofibroblast transdifferentiation trajectory than cells isolated from the right ventricle. Single-cell RNA-sequencing (scRNA-seq) analysis of the two populations confirmed that Postn+ CFs are more enriched in the LV, whereas Igfbp3+ CFs were enriched in the RV at baseline. Notably, following pressure overload injury, the LV developed a larger subpopulation of pro-fibrotic Thbs4+/Cthrc1+ injury-induced CFs, while the RV showed unique expansion of two less-well characterized subpopulations of CFs (Igfbp3+ and Inmt+). These findings demonstrate that LV and RV-derived CFs display baseline subpopulation differences that may dictate their diverging responses to pressure overload injury. Further study of these subpopulations will elucidate their role in the development of fibrosis and inform whether LV and RV fibrosis require distinct treatments.
2024-02-28 | GSE255542 | GEO
Project description:Aims. We sought to analyze the physiological differences of human C-MSC between the left ventricle (LV) versus the right ventricle (RV) . Methods and results. Autoptic cardiac specimens from LV and RV were obtained from healthy donors. Part was used for tissue sections; part was processed to obtain C-MSC. Isogenic LV and RV C-MSC were compared as for surface markers expression, cell proliferation/death ratio, differentiation capabilities and transcriptomics. Our results indicated a greater presence of C-MSC in RV vs. LV total tissue. Moreover, more cells can be obtained from RV than from LV after isolation procedures. LV and RV C-MSC are characterized by the expression of the same surface markers. Functional studies revealed RV-LV C-MSC comparable groth curves but higher apoptosis rate within the LV cells. Moreover, higher propensity of the RV to to collagen deposition was obseved. Transcriptome analysis confirmed differences in the expression of genes related to apoptosis regulation and extracellular matrix organization. Alongside, we unveiled further pathways specifically associated to LV or RV C-MSC. Conclusions. These results contribute to understand the role of RV and LV C-MSC in physiological condition. Moreover, the obtained information can unravel their differential contribution to RV or LV- specific pathologic scenarios. RNA-Seq allowed identifying novel differentially expressed genes in RV vs. LV cells, which might uncover unappreciated mechanisms underlying ventricle-specific C-MSC regulation.
2020-05-01 | GSE142205 | GEO
Project description:Pulmonary arterial hypertension (PAH) is characterized by remodelling of the pulmonary arteries and right ventricle (RV), which leads to functional decline of cardiac and skeletal muscle. This study investigated the effects of a multi-targeted nutritional intervention with extra protein, leucine, fish oil and oligosaccharides on cardiac and skeletal muscle in PAH. PAH was induced in female C57BL/6 mice by weekly injections of monocrotaline (MCT) for 8 weeks. Control diet (sham and MCT group) and isocaloric nutritional intervention (MCT + NI) were administered. Compared to sham, MCT mice increased heart weight by 7%, RV thickness by 13% and fibrosis by 60% (all p < 0.05) and these were attenuated in MCT + NI mice. Microarray and qRT-PCR analysis of RV confirmed effects on fibrotic pathways. Skeletal muscle fiber atrophy was induced (P < 0.05) by 22% in MCT compared to sham mice, but prevented in MCT + NI group. Our findings show that a multi-targeted nutritional intervention attenuated detrimental alterations to both cardiac and skeletal muscle in a mouse model of PAH, which provides directions for future therapeutic strategies targeting functional decline of both tissues.
2019-07-29 | GSE125537 | GEO
Project description:Human cardiac tissue (Apex, LV, RV), whole tissue and isolated cardiomyocyte, processed by s-trap, with and without high pH fractionation, DDA of non-fractionated and fractionated and DIA of non-fractionated
2021-03-25 | MSV000087095 | MassIVE
Project description:The contribution of radiotherapy, per se, in late cardiotoxicity remains controversial. An experimental model was developed, in which rat hearts were exposed to a range of ionizing radiation doses, to clarify its impact on the development of early cardiac dysfunction. Rat’s hearts were exposed to daily doses of 0.04, 0.3 and 1.2 Gy, for 23 days, achieving cumulative doses of 0.92, 6.9 and 27.6 Gy, respectively. Myocardial deformation, assessed by global longitudinal strain, was impaired (a relative percentage reduction of > 15% from baseline) in a dose-dependent manner. Moreover, by scanning electron microscopy, the microvascular density in the cardiac apex was significantly decreased exclusively at 27.6 Gy dosage. Prior to GLS impairment detection, several tools (qRT-PCR, mass spectrometry and western blot) were used to assess cardiac tissue remodeling. The number/expression of several genes, proteins and KEGG pathways, related to inflammation, fibrosis and cardiac muscle contraction, were found to be differently expressed in the cardiac tissue, according to the cumulative dose. Subclinical cardiac dysfunction occurred in a dose-dependent manner as detected by cardiac tissue remodeling, a predictor of the severity of global longitudinal strain impairment. Moreover, there is no dose threshold below which no myocardial deformation impairment was detected. These findings may contribute to i) develop new markers and explore non-invasive magnetic resonance imaging to assess cardiac tissue remodeling as an early predictor of cardiac dysfunction; ii) improve radiation-based diagnostic and therapeutic cardiac procedures; iii) highlight the need for personalized clinical approaches.
2022-09-08 | PXD033194 | Pride
Project description:Affymetrix GeneChip Exon-1.0ST was used to study the differential gene profiles in RV (right ventricle) samples from neonates with HLHS (hypoplastic left heart syndrome) versus RV and LV (left ventricle) samples obtained from age-matched controls. Although few significant changes were observed in the genetic profiles between control LV and control RV, many genes passed the false discovery rate in comparing HLHS-RV to RV and LV control groups, with greater differential profiles noted between HLHS-RV and control RV. Myocardial samples were isolated from the RV of 6 HLHS neonates, diagnosed based upon clinical features including hypoplasia/atresia of the ascending aorta, various degrees of underdevelopment of the aortic valve, mitral valve, and LV cavity, and retrograde flow in the aortic arch as determined by conventional 2-D echocardiography. The mean gestational age at birth of all subjects was 38 weeks (range 36-39) and the mean body weight at surgery of 2.7 kg (range 2.1-3.4 kg) (3 males, 3 females). All subjects were undergoing stage 1 Norwood reconstruction. Children with HLHS and other complex cardiac anomalies entailing non-HLHS single ventricle circulation were excluded from our study. For control samples, RV and LV myocardial tissue was obtained from 5 newborns aged between 1-28 days (mean 18 days; 3 males and 2 females) with normal cardiac anatomy and expired from non-cardiac diseases processes.
2011-12-31 | E-GEOD-23959 | biostudies-arrayexpress