Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Metabolomic Signature of Early Vascular Aging (EVA) in Hypertension

ABSTRACT:

Arterial stiffening is a hallmark of early vascular aging (EVA) syndrome and an independent predictor of cardiovascular morbidity and mortality. In this case-control study we sought to identify plasma metabolites associated with EVA syndrome in the setting of hypertension. An untargeted metabolomic approach was used to identify plasma metabolites in an age-, BMI- and sex-matched groups of EVA (n = 79) and non-EVA (n = 73) individuals with hypertension. After raw data processing and filtration, 497 putative compounds were characterized, out of which 4 were identified as lysophosphaditylcholines (LPCs) [LPC (18:2), LPC (16:0), LPC (18:0) and LPC (18:1)]. A main finding of this study shows that identified LPCs were independently associated with EVA status. Although LPCs have been shown previously to be positively associated with inflammation and atherosclerosis, we observed that hypertensive individuals characterized by 4 down-regulated LPCs had 3.8 times higher risk of EVA compared to those with higher LPC levels (OR = 3.8, 95% CI 1.7 – 8.5, P < .001). Our results provide new insights into a metabolomic phenotype of vascular aging and warrants further investigation of negative association of LPCs with EVA status. This study suggests that LPCs are potential candidates to be considered for further evaluation and validation as predictors of EVA in patients with hypertension

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse phase, Liquid Chromatography MS - positive - reverse phase

SUBMITTER: Renata Bujak

PROVIDER: MTBLS1359 | MetaboLights | 2020-01-14

REPOSITORIES: MetaboLights

ACCESS DATA

Json Xml

Similar Datasets

OPC Cell Culture with LPC 18:1 or LPC 18:1 (both + C13-His)

Project description:Rat OPCs were incubated in the presence of LPC 18:1 or LPC 18:0 and C13-His. Cultures controls included no treatment and a positive control for the differentiation of OPCs. LPC 18:1 was administered at 10 uM while C13-His was administered at 10 uM. Samples were process for mass spectrometry to identify the incorporation of C13-His in newly synthesized proteins.

2022-02-17 | PXD025177 | Pride

Lysophosphatidylcholines activate PPARδ and protect human skeletal muscle cells from lipotoxicity

Project description:Metabolomics studies of human plasma demonstrate a correlation of lower plasma lysophosphatidylcholines (LPC) concentrations with insulin resistance, obesity, and inflammation. This relationship is not unraveled on a molecular level. Here we investigated the effects of the abundant LPC(16:0) and LPC(18:1) on human skeletal muscle cells differentiated to myotubes. Transcriptome analysis of human myotubes treated with 10 µM LPC for 24 h revealed enrichment of up-regulated peroxisome proliferator-activated receptor (PPAR) target transcripts, including ANGPTL4, PDK4, PLIN2, and CPT1A. The increase in both PDK4 and ANGPTL4 RNA expression was abolished in the presence of either PPARδ antagonist GSK0660 or GSK3787. The induction of PDK4 by LPCs was blocked with siRNA against PPARD. The activation of PPARδ transcriptional activity by LPC was shown as PPARδ-dependent luciferase reporter gene expression and enhanced DNA binding of the PPARδ/RXR dimer. On a functional level, further results show that the LPC-mediated activation of PPARδ can reduce fatty acid-induced inflammation and ER stress in human skeletal muscle cells. The protective effect of LPC was prevented in the presence of the PPARδ antagonist GSK0660. Taking together, LPCs can activate PPARδ, which is consistent with the association of high plasma LPC levels and PPARδ-dependent anti-diabetic and anti-inflammatory effects.

2016-10-14 | GSE77337 | GEO

Recapitulation of human premature aging by using iPSCs from Hutchinson-Gilford progeria syndrome

Project description:Hutchinson-Gilford progeria syndrome (HGPS) is a rare and fatal human premature aging disease1-5, characterized by premature atherosclerosis and degeneration of vascular smooth muscle cells (SMCs)6-8. HGPS is caused by a single-point mutation in the LMNA gene, resulting in the generation of progerin, a truncated mutant of lamin A. Accumulation of progerin leads to various aging-associated nuclear defects including disorganization of nuclear lamina and loss of heterochromatin9-12. Here, we report the generation of induced pluripotent stem cells (iPSCs) from fibroblasts obtained from patients with HGPS. HGPS-iPSCs show absence of progerin, and more importantly, lack the nuclear envelope and epigenetic alterations normally associated with premature aging. Upon differentiation of HGPS-iPSCs, progerin and its associated aging consequences are restored. In particular, directed differentiation of HGPS-iPSCs to SMCs leads to the appearance of premature senescent SMC phenotypes associated with vascular aging. Additionally, our studies identify DNA-dependent protein kinase catalytic subunit (DNAPKcs) as a component of the progerin-containing protein complex. The absence of nuclear DNAPKcs correlates with premature as well as physiological aging. Since progerin also accumulates during physiological aging6,12,13, our results provide an in vitro iPSC-based model with an acceleration progerin accumulation to study the pathogenesis of human premature and physiological vascular aging. Microarray gene expression profiling was done to: (1) Compare differences between WT fibroblasts and fibroblasts from patients suffering of the Hutchinson-Gilford progeria syndrome (2) Check that iPSC originating from WT and patients are in fact similar to ESC

2011-03-14 | E-GEOD-24487 | biostudies-arrayexpress

Vucur_et_al

Project description:Comparison of the genomic copy number status of livers from wildtype mice (reference) with Tak1/Casp8 knockout mice or Tak1/LPC knockout mice or Tak1/LPC/RIP3 knockout mice.

2013-07-22 | E-MTAB-1559 | biostudies-arrayexpress

gene expression in monkey aorta with aging and gender

2007-12-27 | GSE6599 | GEO

LPC 18:1 protein interaction (OPC)

Project description:Oligodendrocyte progenitor cells (OPC) were cultured in the presence of LPC 18:1-Cy5. Proteins interacting with LPC 18:1-Cy5 were UV crossed linked and cell lysates were separated via isoelectric focusing gel electrophoresis. Band was cut out from gel and processed for mass spectrometry. OPC lysates were also incubated with LPC 18:1-micelles and allowed to interact with OPC proteins. Samples were separated using sucrose gradient (Liposome floatation assay), top fraction was collected and processed for mass spectrometry.

2022-02-17 | PXD025175 | Pride

Transcription profiling of monkey aorta to examine aging and gender effects

Project description:Although increased vascular stiffness is more prominent in aging males than females, and males are more prone to vascular disease with aging, no study has investigated the genes potentially responsible for gender differences in vascular aging. We tested the hypothesis that the transcriptional adaptation to aging differs in males and females using a monkey model, which is not only physiologically and phylogenetically closer to humans than the more commonly studied rodent models, but also is not afflicted with the most common forms of vascular disease that accompany the aging process in humans, e.g., atherosclerosis, hypertension, and diabetes. Gene expressions of monkey aorta from four groups (YF, OF, YM, OM) were detected to find out the molecular mechanism of aorta stiffness. Experiment Overall Design: Four groups were used in this experiment. 6 samples per group.The transcriptional profile of the aorta was compared by high-density microarrays between young and old males or females. About 600 genes were expressed differentially when comparing old versus young animals. Analysis of the different groups was further performed by gene ontology.We also analyzed whether the transcriptional regulation described above might correspond to specific transcription factors

2008-06-15 | E-GEOD-6599 | biostudies-arrayexpress

Direct reprogramming of fibroblasts identifies signatures of vascular dysfunction in physiological aging and Hutchinson-Gilford Progeria Syndrome

Project description:Our goal was to identify gene expression and functional differences between directly reprogrammed vascular cells derived from young and old individuals, as wells as from healthy and Hutchinson-Gilford Progeria Syndrome (HGPS) donors. We provided a full characterization of reprogrammed endothelial and smooth muscle cells by comparing their gene expression with both the original fibroblasts and primary vascular cells, showing that reprogrammed cells express key vascular cell-identity genes and contribute to the formation of in vitro 3D vascular structures. We identified and validated biomarkers of vascular dysfunction in the context of physiological and accelerated aging typical of HGPS patients, and we demonstrated their direct contribution in the modulation of vascular permeability.

2020-09-03 | GSE140898 | GEO

Epigenome-wide profiling uncovers novel pathway networks in human pulmonary arterial hypertension [pul36]

Project description:Pulmonary arterial hypertension (PAH) is a progressive pulmonary vascular disease that culminates in right heart failure. Vascular pathology in PH is characterized by pulmonary vasoconstriction and progressive vascular remodeling processes that affects all layers of the vascular wall (intima, media and adventitia).

2022-06-09 | GSE194080 | GEO

Progerin Expression in Endothelial Cells Induces Endothelial Dysfunction

Project description:Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare, genetic premature aging disorder associated with severe atherosclerosis, often resulting in fatal heart attacks and strokes. Progerin, the mutant protein in HGPS, also is expressed in healthy individuals and may play a role in the development of atherosclerosis during physiologic aging. Here, we provide evidence for a primary involvement of vascular endothelium in the pathogenesis of accelerated atherosclerosis in HGPS. Expression of progerin in cultured human endothelial cells induces a dysfunctional phenotype, manifested by activation of multiple pro-inflammatory, pro-atherogenic genes. In particular, our data implicate endothelial-derived interleukin-1 (IL-1) as a key mediator of a pro-inflammatory vascular phenotype. Endothelial activation also is detectable in a mouse model of HGPS, and appears to be conveyed to neighboring vascular cells via autocrine and paracrine signaling. These new mechanistic insights into the vascular pathobiology of HGPS may have therapeutic implications for this disease. Genome-wide transcriptional profiling was carried out to assess functional phenotypic changes in endothelial cells (EC) as a result of progerin expression. Cultured EC were infected with an adenovirus expressing progerin (Ad-Progerin), and as a control, an adenovirus that did not express any construct (Ad-Null). Experiments were preformed with three different EC cultures.

2010-12-02 | E-GEOD-19270 | biostudies-arrayexpress

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