Regional differences in left ventricular shear stress contribute to heterogenity of the endocardial transcriptome
Ontology highlight
ABSTRACT:
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR926727_1.fastq.gz | Fastqsanger.gz | |||
| ERR926727_2.fastq.gz | Fastqsanger.gz | |||
| ERR926728_1.fastq.gz | Fastqsanger.gz | |||
| ERR926728_2.fastq.gz | Fastqsanger.gz | |||
| ERR926729_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 48 |
Similar Datasets
Project description:The role of shear stress, the frictional force of blood flow, on the endothelium has been well documented. Differences in shear stress can have profound effects on endothelial and blood vessel biology. Endothelial cells (ECs), termed endocardial ECs, line the heart chambers and are exposed to complex shear stress patterns. While it has been demonstrated that shear stress is important for heart development, little has been shown on the role of shear stress on adult ECs. 4D-MRI studies demonstrate regional differences in blood residence time. We sought to determine the effect of regional differences in endocardial shear stress on the endocardial transcriptome using RNA sequencing (RNA-seq) on 3 different regions (apex, mid-ventricle, outflow tract) from 8 adult pigs, for a total of 24 RNA-seq assays.
2015-12-31 | E-MTAB-3669 | biostudies-arrayexpress
Project description:Regional differences in left ventricular shear stress contribute to heterogenity of the endocardial transcriptome
| PRJEB9690 | ENA
Project description:Non-compaction cardiomyopathy is a devastating genetic disease caused by insufficient consolidation of ventricular wall muscle that can result in inadequate cardiac performance. Despite being the third most common cardiomyopathy, the mechanisms underlying the disease, including the cell types involved, are poorly understood. We have previously shown that endothelial cell-specific deletion of the chromatin remodeller gene Ino80 results in defective coronary vessel development that leads to ventricular non-compaction in embryonic mouse hearts. Here, we used single-cell RNA-sequencing to characterize endothelial and endocardial defects in Ino80-deficient hearts. We observed a pathological endocardial cell population in the non-compacted hearts and identified multiple dysregulated angiocrine factors that dramatically affected cardiomyocyte behaviour. We identified Col15A1 as a coronary vessel-secreted angiocrine factor, down-regulated by Ino80-deficiency, which functioned to promote cardiomyocyte proliferation. Furthermore, mutant endocardial and endothelial cells (ECs) AQ6 up-regulated expression of secreted factors, such as Tgfbi, Igfbp3, Isg15, and Adm, which decreased cardiomyocyte proliferation and increased maturation. These findings support a model where coronary ECs normally promote myocardial compaction through secreted factors, but that endocardial and ECs can secrete factors that contribute to non-compaction under pathological conditions.
2021-12-30 | GSE175589 | GEO
Project description:Continuous-flow left ventricular assist devices commonly lead to aortic regurgitation, which results in decreased pump efficiency and worsening heart failure. We hypothesized that non-physiological wall shear stress and oscillatory shear index alter the abundance of structural proteins in aortic valves of left ventricular assist device (LVAD) patients. Doppler images of aortic valves of patients undergoing heart transplants were obtained. Eight patients had been supported with LVADs, whereas 10 were not. Aortic valve tissue was collected and protein levels were analyzed using mass spectrometry. Echocardiographic images were analyzed and wall shear stress and oscillatory shear index were calculated. The relationship between normalized levels of individual proteins and in vivo echocardiographic measurements was evaluated. Of the 57 proteins of interest, there was a strong negative correlation between levels of 15 proteins and the wall shear stress (R < -0.500, p ? 0.05), and a moderate negative correlation between 16 proteins and wall shear stress (R ?0.500 to ?0.300, p ? 0.05). Gene ontology analysis demonstrated clusters of proteins involved in cellular structure. Proteins negatively correlated with WSS included those with cytoskeletal, actin/myosin, cell-cell junction and extracellular functions. In aortic valve tissue, 31 proteins were identified involved in cellular structure and extracellular junctions with a negative correlation between their levels and wall shear stress. These findings suggest an association between the forces acting on the aortic valve (AV) and leaflet protein abundance, and may form a mechanical basis for the increased risk of aortic leaflet degeneration in LVAD patients.
2021-02-23 | MSV000086941 | MassIVE
Project description:We used single cell RNA sequencing (scRNAseq) to show that ventricular endocardial cells generate trabecular vessels through an angioEMT mechanism.
2023-03-07 | GSE205394 | GEO
Project description:Left ventricular noncompaction (LVNC) Causes prominent ventricular trabeculations and reduces cardiac systolic function. The clinical presentation of LVNC ranges from asymptomatic to heart failure. We show that germline mutations in human MIB1 (mindbomb homolog 1), which encodes an E3 ubiquitin ligase that promotes endocytosis of the NOTCH ligands DELTA and JAGGED, cause LVNC in autosomal-dominant pedigrees, with affected individuals showing reduced NOTCH1 activity and reduced expression of target genes. Functional studies in cells and zebrafish embryos and in silico modeling indicate that MIB1 functions as a dimer, which is disrupted by the human mutations. Targeted inactivation of Mib1 in mouse myocardium causes LVNC, a phenotype mimicked by inactivation of myocardial Jagged1 or endocardial Notch1. Myocardial Mib1 mutants show reduced ventricular Notch1 activity, expansion of compact myocardium to proliferative, immature trabeculae and abnormal expression of cardiac development and disease genes. These results implicate NOTCH signaling in LVNC and indicate that MIB1 mutations arrest chamber myocardium development, preventing trabecular maturation and compaction. RNA was isolated from the ventricles of 16 WT and 16 Mib1flox; CTnT-cre hearts at E14.5 and then pooled into four replicates.
2015-08-10 | E-GEOD-71912 | biostudies-arrayexpress
Project description:The ang1-Tie2 pathway is required for normal vascular development, but its molecular effectors are not well-defined during cardiac ontogeny. Here we show that endocardial specific attenuation of Tie2 results in mid-gestation lethality due to heart defects associated with a hyperplastic but simplified trabecular meshwork (fewer but thicker trabeculae). Reduced proliferation and production of endocardial cells (ECs) following endocardial loss of Tie2 results in decreased endocardial sprouting required for trabecular assembly and extension. The hyperplastic trabeculae result from enhanced proliferation of trabecular cardiomyocyte (CMs), which is associated with upregulation of Bmp10, increased retinoic acid (RA) signaling, and Erk1/2 hyperphosphorylation in the myocardium. Intriguingly, myocardial phenotypes in Tie2-cko hearts could be partially rescued by inhibiting in utero RA signaling with pan-retinoic acid receptor antagonist BMS493. These findings reveal two complimentary functions of endocardial Tie2 during ventricular chamber formation: ensuring normal trabeculation by supporting EC proliferation and sprouting, and preventing hypertrabeculation via suppression of RA signaling in trabecular CMs.
2019-05-07 | GSE130741 | GEO
Project description:Left ventricular noncompaction (LVNC) Causes prominent ventricular trabeculations and reduces cardiac systolic function. The clinical presentation of LVNC ranges from asymptomatic to heart failure. We show that germline mutations in human MIB1 (mindbomb homolog 1), which encodes an E3 ubiquitin ligase that promotes endocytosis of the NOTCH ligands DELTA and JAGGED, cause LVNC in autosomal-dominant pedigrees, with affected individuals showing reduced NOTCH1 activity and reduced expression of target genes. Functional studies in cells and zebrafish embryos and in silico modeling indicate that MIB1 functions as a dimer, which is disrupted by the human mutations. Targeted inactivation of Mib1 in mouse myocardium causes LVNC, a phenotype mimicked by inactivation of myocardial Jagged1 or endocardial Notch1. Myocardial Mib1 mutants show reduced ventricular Notch1 activity, expansion of compact myocardium to proliferative, immature trabeculae and abnormal expression of cardiac development and disease genes. These results implicate NOTCH signaling in LVNC and indicate that MIB1 mutations arrest chamber myocardium development, preventing trabecular maturation and compaction.
2015-08-10 | GSE71912 | GEO
Project description:We established a differentiation strategy to generate endocardial-like cells from hPSCs. Endocardial-like cells generated from our protocol display major functional properties of endocardium in developing embryo: they can induce trabecular markers in early hPSC-derived ventricular cardiomyocytes and they can undergo endothelial-to-mesenchymal-trasition under appropriate conditions. Furthermore, the transcriptome of our in vitro generated endocardial cells showed a very high level of correlation to that of primary fetal endocardial cells. Functional properties and transcriptional profile of hPSC-derived endocardial cells were also compared to those of control (non-endocardial) endothelial cells. For scRNA-seq analysis live cells from bulk endocardial and control endothelial differentiation cultures were labeled with two different sets of anti-human Hashtag antibodies before sequencing. Single cell RNA sequencing was carried out on a sample consisting of 85% bulk endocardial cells (TotalSeq-A0255 anti-human Hashtag 5 antibody, BioLegend) and 15% bulk control endothelial cells (TotalSeq-A0254 anti-human Hashtag 4, Biolegend).
2020-11-02 | GSE151186 | GEO
Project description:BackgroundUnlike arteries, in which regionally distinct hemodynamics are associated with phenotypic heterogeneity, the relationships between endocardial endothelial cell phenotype and intraventricular flow remain largely unexplored. We investigated regional differences in left ventricular wall shear stress and their association with endocardial endothelial cell gene expression.Methods and resultsLocal wall shear stress was calculated from 4-dimensional flow magnetic resonance imaging in 3 distinct regions of human (n=8) and pig (n=5) left ventricle: base, adjacent to the outflow tract; midventricle; and apex. In both species, wall shear stress values were significantly lower in the apex and midventricle relative to the base; oscillatory shear index was elevated in the apex. RNA sequencing of the endocardial endothelial cell transcriptome in pig left ventricle (n=8) at a false discovery rate ≤10% identified 1051 genes differentially expressed between the base and the apex and 327 between the base and the midventricle; no differentially expressed genes were detected at this false discovery rate between the apex and the midventricle. Enrichment analyses identified apical upregulation of genes associated with translation initiation including mammalian target of rapamycin, and eukaryotic initiation factor 2 signaling. Genes of mitochondrial dysfunction and oxidative phosphorylation were also consistently upregulated in the left ventricular apex, as were tissue factor pathway inhibitor (mean 50-fold) and prostacyclin synthase (5-fold)-genes prominently associated with antithrombotic protection.ConclusionsWe report the first spatiotemporal measurements of wall shear stress within the left ventricle and linked regional hemodynamics to heterogeneity in ventricular endothelial gene expression, most notably to translation initiation and anticoagulation properties in the left ventricular apex, in which oscillatory shear index is increased and wall shear stress is decreased.
| S-EPMC4859290 | biostudies-literature