Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Deep transcriptomic analysis of human vascular cells identifies novel risk genes for common vascular diseases

ABSTRACT: Several genome-wide association studies have to date been carried out to identify genetic risk loci associated with vascular diseases. Many of the established common variants likely perturb the expression of disease-relevant genes within the vascular tissue itself. To identify such genes on a genome-wide level, we analyzed the transcriptome of human coronary artery smooth muscle and endothelial cells for Allele-Specific Expression (ASE).

ORGANISM(S): Homo sapiens

PROVIDER: GSE111120 | GEO | 2019/12/11

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

FOXO3a functions as a transcriptional and co-transcriptional splicing regulator in vascular endothelial cell lines in coronary artery disease

Project description:Vascular endothelial cells play an important role in the development of coronary artery disease, their injury leads to coronary heart disease and atherosclerosis. This study aimed to elucidate the role of FOXO3-regulated target gene expression and alternative splicing in vascular endothelial cell injury in coronary artery disease

2024-02-09 | GSE225605 | GEO

FHL5 cofactor mediates vascular disease risk by regulating smooth muscle cell transcriptional networks [RNA-seq]

Project description:Genome-wide association studies (GWAS) have identified hundreds of loci associated with vascular diseases such as coronary artery disease (CAD) and myocardial infarction (MI), and hypertension. However, the biological roles for many of these loci enriched in the vessel wall remains unknown. Among these, UFL1-FHL5 (chr6q16.1) emerged as a genome-wide significant locus in a recent CAD/MI meta-analysis. Here, we use an integrative approach leveraging human genetics, epigenomic profiling, and in vitro functional and ex vivo imaging analyses to prioritize FHL5 as the top candidate causal gene and reveal the molecular mechanisms of its pleiotropic genetic associations. Notably, FHL5 overexpression in coronary artery smooth muscle cells (SMC) increased vascular calcification and dysregulated processes related to extracellular matrix organization and calcium handling. Lastly, by mapping FHL5 binding sites genome-wide using CUT&RUN, we identified regulatory interactions with downstream disease loci having putative roles in SMC phenotypic modulation. Together, these trans-acting mechanisms may account for a portion of the heritable risk for CAD/MI and other complex vascular diseases.

2022-10-31 | GSE201571 | GEO

FHL5 cofactor mediates vascular disease risk by regulating smooth muscle cell transcriptional networks [CUT&RUN]

2022-10-31 | GSE201570 | GEO

Proteomic profiling of tissue-engineered, small-diameter vascular grafts implanted into the ovine carotid artery

Project description:Albeit vascular prostheses for the replacement of large arteries (e.g. aorta) are commercially available for decades, small-diameter vascular grafts (e.g., for coronary artery bypass graft surgery) still remain an unmet clinical need. Biostable polymers commonly used for the fabrication of aortic prostheses (e.g., poly(ethylene terephthalate) or expanded poly(tetrafluoroethylene)) have insufficient haemocompatibility to withstand thrombosis at low blood flow characteristic of small arteries (e.g., coronary artery). Hence, researchers endeavor to develop a biodegradable, tissue-engineered vascular graft (TEVG) to avoid the use of autologous blood vessels, such as saphenous vein or internal mammary artery, as conduits during the bypass surgery. Although a number of promising prototypes have been designed to date, none of them passed the pre-clinical trials successfully. Implantation into the ovine or porcine arteries is associated with thrombosis, neointimal hyperplasia, and aneurysms within one-year postoperation, precluding further clinical translation of TEVGs. Among the reasons of such impediment is that pathophysiology of TEVG implantation remains unclear and the molecular events occurring in the TEVG upon its implantation have not been properly investigated hitherto. Here, we for the first time performed a proteomic profiling of the TEVGs (n = 12) implanted into the ovine carotid arteries for one year and suffered from thrombosis to identify the signatures of TEVG failure in an unbiased manner. Contralateral intact ovine carotid arteries (n = 12) have been selected as a control group.

2022-11-26 | PXD036520 | Pride

Carnitine O-octanoyltransferase is a novel inducer of vascular calcification via promoting fatty acid metabolism and mitochondrial dysfunction

Project description:Objective – Vascular calcification is a critical pathology associated with increased cardiovascular event risk, but there are no FDA-approved anti-calcific therapies. We hypothesized and validated that an unbiased screening approach would identify novel mediators of human vascular calcification. Approach and Results – We performed an unbiased quantitative proteomics and pathway network analysis that identified increased carnitine O-octanoyltransferase (CROT) in calcifying primary human coronary artery smooth muscle cells (SMCs). Additionally, human carotid artery atherosclerotic plaques contained increased immunoreactive CROT near calcified regions. CROT siRNA reduced fibrocalcific response in calcifying SMCs. In agreement, histidine 327 to alanine point mutation inactivated human CROT fatty acid metabolism enzymatic activity and suppressed SMC calcification. CROT siRNA restored mitochondrial proteome alterations and suppressed mitochondrial fragmentation in calcifying SMCs. Lipidomics analysis of SMCs incubated with CROT siRNA revealed increased eicosapentaenoic acid, a vascular calcification inhibitor. CRISPR/Cas9-mediated Crot deficiency in low-density lipoprotein receptor-deficient mice reduced aortic and carotid artery calcification without altering bone density, or liver and plasma cholesterol and triglyceride concentrations. Conclusions – CROT is a novel inducer of vascular calcification via promoting fatty acid metabolism and mitochondrial dysfunction, as such CROT inhibition has strong potential as an anti-fibrocalcific therapy.

2021-02-26 | PXD022575 | Pride

Deep transcriptomic analysis of human vascular cells identifies novel risk genes for common vascular diseases

Project description:Deep transcriptomic analysis of human vascular cells identifies novel risk genes for common vascular diseases

| PRJNA435966 | ENA

Locational memory of macrovessel vascular cells is transcriptionally imprinted

Project description:The locational predisposition of vascular pathologies illustrates the need for a better insight into vascular heterogeneity. To investigate the transcriptomic basis of angiodiversity, we isolated and analyzed transcriptomes from endothelial cells and vascular smooth muscle cells from nine different adult canine macrovessels: the aorta, coronary artery, vena cava, portal vein, femoral artery, femoral vein, saphenous vein, pulmonary vein, and pulmonary artery. We identified both reported and novel expression patterns defining specialized adult blood vessels. Our findings also show that adult vascular cells in culture express a remarkably high number of transcription factors crucial to organ development in the embryo. The persistent expression of these genes in culture indicates that these genes are not regulated by the flow or surrounding cell types but are rather fixed in the molecular memory. Therefore, our findings prompt the re-thinking of the extrapolation of results from single-origin endothelial cell systems.

2023-08-22 | GSE171437 | GEO

Transcriptional profiling of osteogenic medium calcified human primary coronary artery smooth muscle cells.

Project description:Transcriptomics analysis of human coronary artery smooth muscle cells cultured in osteogenic medium (OM) to induce a mineralized extracellular matrix. To study the underlying molecular mechanisms driving vascular calcification, we analyzed the transcriptome of osteogenic medium (OM)-calcified human coronary artery smooth muscle cells on day 7.

2022-09-18 | GSE211722 | GEO

Mining the stiffness-sensitive transcriptome in human vascular smooth muscle cells identifies long non-coding RNA stiffness regulators

Project description:Vascular extracellular matrix (ECM) stiffening is a risk factor for aortic and coronary artery disease. How matrix stiffening regulates the transcriptome profile of human aortic (Ao) and coronary (Co) vascular smooth muscle cells (VSMCs) is not well understood. Furthermore, the role of long non-coding RNAs (lncRNAs) in the cellular response to stiffening has never been explored. This study characterizes the stiffness-sensitive transcriptome of human Ao and Co VSMCs and identify potentially key lncRNA regulators of stiffness-dependent VSMC functions. Ao and Co VSMCs were cultured on hydrogel substrates mimicking physiologic and pathologic ECM stiffness. Total RNA-seq was performed to compare the stiffness-sensitive transcriptome profiles of Ao and Co VSMCs.

2017-12-01 | GSE100081 | GEO

MCM8 mediated mitophagy protects vascular health in response to nitric oxide signaling in a mouse model of Kawasaki disease

Project description:Mitophagy is a major quality control pathway that removes unwanted or dysfunctional mitochondria, and plays an essential role in vascular health. Here we show that MCM8 expression is significantly decreased in children with Kawasaki disease (KD) who developed coronary artery aneurysms. Mechanistically, we discover that nitric oxide (NO) signaling promotes TRIM21 mediated MCM8 ubiquitination, which disrupts its interaction with MCM9 and promotes its cytosolic export. In the cytosol, MCM8 relocates to the mitochondria pore forming proteins and promotes their ubiquitination by TRIM21. In addition, MCM8 directly recruits LC3 via its LIR motif and initiates mitophagy. This suppresses mitochondrial DNA-mediated activation of type I interferon via cGAS and STING. Mice that are deficient in Mcm8, Trim21, Nos2, or reconstituted with the East-Asian specific MCM8-P276 variant develop more severe coronary artery vasculopathy in the Lactobacillus casei extract-induced KD model. Collectively, the data suggest that MCM8 protects vascular health in the KD setting.

2023-06-29 | GSE235994 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data