RNA sequencing of cardiac endothelial cells from the cardiovascular disease risk factor mouse models
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE145263 | GEO | 2020/10/31
REPOSITORIES: GEO
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Project description:RNA sequencing of cardiac endothelial cells from the cardiovascular disease risk factor mouse models
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Project description:The cytochrome P450 reductase (POR) transfers electrons to all microsomal cytochrome P450 enzymes (CYP450) thereby driving their activity. In the vascular system, the POR/CYP450 system has been linked to the production of epoxyeicosatrienoic acids (EETs) but also to the generation of reactive oxygen species. In cardiac myocytes (CMs), EETs have been shown to modulate the cardiac function and have cardioprotective effects. The functional importance of the endothelial POR/CYP450 system in the heart is unclear and was studied here using endothelial cell-specific, inducible knockout mice of POR (ecPOR-/-). RNA sequencing of murine cardiac cells revealed a cell type-specific expression of different CYP450 homologues. Cardiac endothelial cells mainly expressed members of the CYP2 family which produces EETs, and of the CYP4 family that generates omega fatty acids. Tamoxifen-induced endothelial deletion of POR in mice led to cardiac remodelling under basal conditions, as shown by an increase in heart weight to body weight ratio and an increased CM area as compared to control animals. Endothelial deletion of POR was associated with a significant increase in endothelial genes linked to protein synthesis with no changes in genes of the oxidative stress response. CM of ecPOR-/- mice exhibited attenuated expression of genes linked to mitochondrial function and an increase in genes related to cardiac myocyte contractility. In a model of pressure overload (transverse aortic constriction, TAC with O-rings), ecPOR-/- mice exhibited an accelerated reduction in cardiac output (CO) and stroke volume (SV) as compared to control mice. These results suggest that loss of endothelial POR along with a reduction in EETs leads to an increase in vascular stiffness and loss in cardioprotection, resulting in cardiac remodelling.
2022-12-21 | GSE214776 | GEO
Project description:Dysplasia of cardiac endothelial cells significantly contributes to congenital heart disease (CHD), the most common congenital disability. The regulatory role of miRNAs in this process remains elusive. This study identified elevated miR-187 expression in embryonic heart endothelial cells from CHD fetuses. Using a conditional knock-in model, we showed that increased miR-187 levels in embryonic endothelial cells induce CHD in homozygous fetal mice, closely mirroring human CHD. Mechanistically, miR-187 targets NIPBL, which is responsible for recruiting the cohesin complex and facilitating chromatin accessibility between enhancers and promoters. Consequently, the endothelial cell-specific upregulation of miR-187 inhibited NIPBL, leading to reduced chromatin accessibility and impaired gene expression, which hindered endothelial cell development and ultimately caused heart septal defects and reduced heart size both in vitro and in vivo. Importantly, exogenous miR-187 expression in human cardiac organoids mimicked developmental defects in the cardiac endothelial cells, reversible by NIPBL replenishment. Our findings establish the miR-187/NIPBL axis as a potent regulator that inhibits cardiac endothelial cell development by attenuating the transcription of numerous endothelial genes, with our mouse and human cardiac organoid models effectively replicating severe defects from minor perturbations.
2024-11-03 | GSE275849 | GEO
Project description:Cardiac endothelial RNA from Tie-2 GFP mice exposed to intraperitoneal LPS vs. saline, 4 h. RNA amplified 2 rounds. Experiment and dye reversal with cy5, cy3.
2010-06-09 | E-GEOD-1038 | biostudies-arrayexpress
Project description:Accumulation of activated cardiac fibroblasts plays a key role in heart failure progression. These cells deposit excessive extracellular matrix that leads to mechanical stiffness, myocyte uncoupling and ischemia. To investigate whether two developmentally distinct cardiac fibroblast populations exhibit distinct expression profiles in response to cardiac injury, and therefore might necessitate distinct therapeutic targeting, we performed microarray analysis on FACS sorted cells. Tie2cre lineage traced CFs, non Tie2cre lineage traced cardiac fibroblasts and endothelial cells were isolated from left ventricle of SHAM operated and banded hearts at the onset of fibrosis, one week after surgery. We used microarrays to detail the global programme of gene expression in cardiac fibroblasts and endothelium following pressure overload. Tie2cre lineage traced, non-tie2cre lineage traced fibroblasts and endothelial cells were sorted from left ventricle of 3 SHAM operated and 3 TAC operated adult male Black Swiss mice. Tie2cre lineage traced, non-tie2cre lineage traced fibroblasts and endothelial cells were sorted from left ventricle of 3 SHAM operated and 3 Transaortic Constriction (TAC) operated adult male Black Swiss mice for RNA extraction and Affymetrix microarray analysis. Hypertrophy in TAC animals, an lack of hypertrophy in SHAM operated animals, was evaluated by hemodynamic measurements before surgery and one week after surgery. Cells were isolated one week after surgery.
2014-05-19 | E-GEOD-45820 | biostudies-arrayexpress
Project description:Developmental transcriptome profiling of cardiac vascular endothelial subsets
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Project description:Age-Dependent Transcriptional Alterations in Cardiac Endothelial Cells
| PRJNA687680 | ENA
Project description:Purpose: The goal of this study is to determine alterations in heart endothelial cell transcripts associated with aging. This is accomplished by comparing endothelial transcriptomes from young and aged organs (heart, brain and kidney). Methods: Endothelial mRNA profiles of 3 month and 24 month old wild-type mice were generated by next generation sequencing using libraries generated via SmartSeq V4 chemistry (Takara) and sequenced on an HiSeq 2500 (Illuina). Tophat2 with default parameters was used to align the sequenced reads against the mouse genome using the GRCm38. HTSeq python software with default parameters was used to quantify the transcripts of the aligned reads using the corresponding GRCm38 gene annotation model from Ensembl. Results: Highly enriched populations of endothelial cells (ECs) isolated from the heart, brain and kidney of young (3 months) and old (24 months) C57/BL6 mice were profiled for RNA expression via bulk RNA sequencing. Approximately 700 cardiac endothelial transcripts significantly differ by age. Gene set enrichment analysis indicated similar patterns for cellular pathway perturbations. Receptor-ligand comparisons indicated parallel alterations in age-affected circulating factors and cardiac endothelial-expressed receptors. Single-cell RNA-seq analysis identified 9 distinct endothelial cell subtypes in the heart with an age-associated population shift observed for an Aplnr-enriched endothelial cell clusters. Conclusions: Gene and pathway enrichment analyses show that age-related transcriptional response of cardiac endothelial cells is distinct from that of endothelial cells derived from the brain or kidney vascular bed. Furthermore, single-cell analysis identified 9 distinct EC subtypes, and shows that Aplnr-enriched subtype is reduced with age in mouse heart. Finally, we identify age-dysregulated genes in specific aged cardiac endothelial subtypes.
2021-05-28 | GSE163821 | GEO
Project description:Transcriptional responses of cardiac endothelial cells isolated from Tie-2 GFP mice 4 h and 24 h after intraperitoneal LPS injection. Operon V1 long oligo set. Hybridization using Cy3 and Cy5 labeled amplified RNA. Keywords: parallel sample
2004-02-26 | GSE1042 | GEO
Project description:Neuregulin-1 (NRG1) is a paracrine growth factor, secreted by cardiac endothelial cells (Ecs) in conditions of cardiac overload/injury. The current concept is that the cardiac effects of NRG1 are mediated by activation of ERBB4/ERBB2 receptors on cardiomyocytes. However, recent studies have shown that paracrine effects of NRG1 on fibroblasts and macrophages are equally important. Here, we hypothesize that NRG1 autocrine signaling plays a role in cardiac remodeling. We generated EC–specific Erbb4 knockout mice to eliminate endothelial autocrine ERBB4 signaling without affecting paracrine NRG1/ERBB4 signaling in the heart. We first observed no basal cardiac phenotype in these mice up to 32 weeks. We next studied these mice following transverse aortic constriction (TAC), exposure to angiotensin II (Ang II) or myocardial infarction in terms of cardiac performance, myocardial hypertrophy, myocardial fibrosis and capillary density. In general, no major differences between EC–specific Erbb4 knockout mice and control littermates were observed. However, 8 weeks following TAC both myocardial hypertrophy and fibrosis were attenuated by EC–specific Erbb4 deletion, albeit these responses were normalized after 20 weeks. Similarly, 4 weeks after Ang II treatment myocardial fibrosis was less pronounced compared to control littermates. These observations were supported by RNA-sequencing experiments on cultured endothelial cells showing that NRG1 controls the expression of various hypertrophic and fibrotic pathways. Overall, this study shows a role of endothelial autocrine NRG1/ERBB4 signaling in the modulation of hypertrophic and fibrotic responses during early cardiac remodeling. This study contributes to understanding the spatio-temporal heterogeneity of myocardial autocrine and paracrine responses following cardiac injury.
2020-05-15 | GSE150619 | GEO