Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Oxysterol Sensing through GPR183 Triggers Endothelial Senescence and Cardio-renal Injuries via Altering Circadian Signaling in Hypertension

ABSTRACT: Background: Despite endothelial dysfunction being considered as the initial step of the development of hypertension and associated cardio-renal syndromes, effective therapeutic strategies to prevent endothelial injuries are still lacking. GPR183 is a recently identified GPCR for oxysterols and hydroxylated metabolites of cholesterol. Here, we explored a previously unappreciated role of GPR183 in hypertension and age-related cardio-renal injuries. Methods and results: Mice were treated with DOCA/Salt or AngII to induce hypertension. we found that endothelial GPR183 was significantly induced in aged or hypertensive mice, which was further confirmed in renal biopsies from elderly people or subjects with hypertensive nephropathy. In addition, we found that endothelial-specific GPR183 deletion markedly ameliorated endothelial senescence and cardio-renal injuries in hypertensive mice. Mechanistically, we found that GPR183 disrupted circadian signaling by inhibiting PER1 expression, thereby facilitating endothelial senescence and dysfunction through the cAMP/PKA/CREB signaling pathway. Importantly, pharmacological inhibition of the oxysterol-GPR183 axis by NIBR189 or Clotrimazole ameliorated endothelial senescence and cardio-renal injuries in hypertensive mice. Conclusions: GPR183 is an attractive therapeutic target for hypertension and age-related diseases. Targeting GPR183 could provide novel strategies for managing hypertension and its associated cardio-renal injuries.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE270175 | GEO | 2024/06/23

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Oxysterol Sensing through GPR183 Triggers Endothelial Senescence and Cardio-renal Injuries via Altering Circadian Signaling in Hypertension

Project description:Oxysterol Sensing through GPR183 Triggers Endothelial Senescence and Cardio-renal Injuries via Altering Circadian Signaling in Hypertension

| PRJNA1125379 | ENA

Protective mechanisms of Qingda granule in hypertensive kidney injury: Focus on ERK/RSK1-mediated mitochondrial protection

Project description:The objective of this study was to compare blank control mice (WT) with AngII-induced hypertensive mice (M). Angii-induced hypertensive mice (M) and QDG intervention group (QDG); Different genes expressed in renal tissue and identify new targets for reversing hypertension-induced renal damage.

2024-11-12 | GSE281114 | GEO

Endothelial Transcriptome Remodeling in a Mouse Model of Chronic Hypertension

Project description:Aims: Hypertension poses a significant challenge to vasculature homeostasis and stands as the most common cardiovascular disease in the world. Its effects are especially profound on vasculature-lining endothelial cells that are directly exposed to the effects of excess pressure. Here, we characterize the in vivo transcriptomic response of cardiac endothelial cells to hypertension using the spontaneous hypertension mouse model BPH/2J. Methods and results: Verification of defective endothelial function in the BPH/2J hypertensive mouse strain was followed by acute isolation of cardiac endothelial cells and transcriptional profiling using RNA sequencing. Gene profiles from normotensive BPN/3J mice were compared to hypertensive animals. We observed over 3000 transcriptional differences between groups including pathways consistent with the cardiac fibrosis found in hypertensive animals. Importantly, many of the fibrosis-linked genes also differ between juvenile pre-hypertensive and adult hypertensive BPH/2J mice, suggesting that these transcriptional differences are hypertension-related. We also show that blood pressure normalization with amlodipine resulted in a subset of genes reversing their expression pattern, supporting the hypertension-dependency of altered gene expression. Yet, other transcripts were recalcitrant to therapeutic intervention illuminating the possibility that hypertension may irreversibly alter some endothelial transcriptional patterns. Conclusions: Hypertension has a profound effect on both function and transcription of endothelial cells, the latter of which was only partially restored with normalization of blood pressure. This study represents one of the first to quantify how endothelial cells are reprogrammed at the molecular level in cardiovascular pathology and advances our understanding of the transcriptional events associated with endothelial dysfunction.

2018-04-09 | GSE104530 | GEO

Comparative proteomic analysis in microdissected renal vessels of hypertensive and normotensive rats

Project description:Systemic hypertension has a profound impact on the renal vascular physiology. In order to elucidate the biological pathways and macromolecules deregulated by hypertension renal vessels were obtained by Laser Capture Microdissection (LCM) from Spontaneously Hypertensive Rats (SHR) and age-matched controls (20 weeks). Proteomic analysis was performed aiming to detect early molecular alterations associated with hypertension at the renal vessels before the onset of vascular damage. Proteomic analysis identified 688 proteins, of which 58 were differentially expressed (15 up-regulated and 43 down-regulated in SHR). Many of these proteins are involved in vascular tone regulation by modulating the activity of endothelial Nitric Oxide Synthase (eNOS) (e.g. Xaa-Pro aminopeptidase 1 (XPP1), N(G) N(G)-dimethylarginine dimethylaminohydrolase 1 (DDAH1), Dehydropteridine reductase (DHPR)) or in blood pressure control by regulating the renin-angiotensin system (e.g. Glutamyl aminopeptidase/Aminopeptidase A (AMPE), Aminopeptidase N (AMPN)). Moreover, pathway enrichment analysis revealed that the eNOS activation pathway is deregulated only in SHR. Our study demonstrates that hypertension causes early proteomic changes in the renal vessels of SHR. These changes are relevant to vascular tone regulation and consequently may be involved in the development of vascular damage and hypertensive nephrosclerosis. Therefore, the identified proteins could be considered as therapeutic targets.

2022-03-03 | PXD008792 | Pride

Podocytes from Hypertensive and Obese Mice Acquire an Inflammatory, Senescent and Aged Phenotype

Project description:Patients with hypertension or obesity can develop glomerular dysfunction characterized by injury and depletion of podocytes. To better understand the molecular processes involved, young mice were treated with either deoxycorticosterone acetate (DOCA) or fed a high-fat diet (HFD) to induce hypertension or obesity, respectively. The transcriptional changes associated with these phenotypes were measured by unbiased bulk mRNA-sequencing of isolated podocytes from experimental models and their respective controls. Key findings were validated by immunostaining. In addition to a decrease in canonical proteins and reduced podocyte number, podocytes from both hypertensive and obese mice exhibited a sterile inflammatory phenotype characterized by increases in NLRP3 inflammasome, protein cell death-1, and Toll-Like Receptor pathways. Finally, although the mice were young, podocytes in both models exhibited increased expression of senescence and aging genes, including genes consistent with a senescence-associated secretory phenotype. However, there were differences between the hypertension- and obesity-associated senescence phenotypes. Both show stress-induced podocyte senescence characterized by increased p21 and p53. Moreover, in hypertensive mice, this is superimposed upon age-associated podocyte senescence characterized by increased p16 and p19. These results suggest that senescence, aging, and inflammation are critical aspects of the podocyte phenotype in experimental hypertension and obesity in mice.

2024-07-03 | GSE255723 | GEO

Vascular bed systematic profiling unravels endothelial and glycocalyx dysregulations in experimental high salt hypertension

Project description:Objective: Considerable evidence links dietary salt intake with the development of hypertension, left ventricular hypertrophy, and increased risk of stroke and coronary heart disease. Despite extensive epidemiological and basic science interrogation of the relationship between high salt (HS) intake and blood pressure, it remains unclear how HS impacts endothelial cell (EC) and vascular structure in vivo. This study aims to uncover the HS-induced vascular pathologies using a differential systemic decellularization in vivo (DISDIVO) approach.Approach and Results: We performed systematic molecular characterization of the endothelial glycocalyx (eGC) and EC proteomes in mice with HS (8%) diet-induced hypertension versus healthy control animals. Isolation of eGC and ECs compartments was achieved using the DISDIVO approach. Altered protein expression in hypertensive compared to normal mice was characterized by liquid chromatography tandem-mass spectrometry (LC-MS/MS). Proteomic results from eGC fractions revealed a significant downregulation of eGC and associated proteins in HS diet-induced hypertensive mice. Among 1696 proteins identified in this group, 723 were markedly downregulated while 168 were upregulated, bioinformatic analysis indicates critical damage and derangement of eGC layer. In the ECs fraction HS-induced hypertension significantly altered protein mediators of contractility, metabolism, mechanotransduction, renal functions, and coagulation cascades. In particular, we observed dysregulation of integrin subunits alpha2, alpha2b, and alpha5, which relay external signals to the actin cytoskeleton.Conclusion: These findings provide novel molecular insight on HS-induced structure changes in eGC and ECs that may increase cardiovascular risk and potentially guide the development of new diagnostics and therapeutic interventions.

2023-10-24 | PXD031228 | Pride

Alteration and Reprogramming of Renal Ptger1 DNA Methylation Induced by Maternal Protein Restriction in SHRSP Offspring

Project description:Nutrient imbalances during gestation are a risk factor for hypertension in offspring. In this study, we found that, in spontaneously hypertensive stroke-prone (SHRSP) rats, maternal protein restriction during gestation modulates the DNA methylation status and significantly upregulates the expression of renal prostaglandin E receptor 1 (Ptger1), which is associated with hypertension in offspring. Renal Ptger1 DNA methylation is characterized by hypermethylation of CpG islands within the gene and a tendency toward hypomethylation in promoter regions. Furthermore, we observed that changes in fetal Ptger1 DNA methylation status after birth were preserved and enhanced, strongly supporting the stable conservation of this epigenetic marker. However, post-weaning low- or high-protein diets ameliorated Ptger1 DNA hypermethylation caused by fetal malnutrition, indicating postnatal nutritional environment interventions can alter and reprogram epigenetic modifications. These findings provide new insights into hypertension prevention and prospective therapeutic strategies.

2023-10-04 | GSE216424 | GEO

Up-regulation of prolactin receptor in the proximal tubular cells in cardio-renal syndrome model mice

Project description:The precise physiological mechanisms of cardio-renal syndrome are yet to be elucidated. In order to investigate the molecular basis of cardio-renal syndrome, we established a mouse model for cardio-renal syndrome by the combination of abdominal aortic banding and uninephrectomy. Renal function of the cardio-renal syndrome mice was synergistically decreased compared with that of mice that underwent uninephrectomy alone. To investigate the molecules involved in the deterioration renal function in the AbNx mice, we conducted comprehensive gene expression analysis using DNA array by comparing the molecules expressed in the remained kidney of AbNx mice with those of Nx mice.

2012-03-19 | GSE36591 | GEO

Up-regulation of prolactin receptor in the proximal tubular cells in cardio-renal syndrome model mice

2012-03-19 | E-GEOD-36591 | biostudies-arrayexpress

Inflammatory Alterations to Renal Lymphatic Endothelial Cell Gene Expression in Mouse Models of Hypertension

Project description:To evaluate the specific changes that renal LECs undergo in hypertension (HTN), we performed single-cell RNA sequencing. Using the angiotensin II-induced and salt-sensitive mouse models of HTN, we isolated renal CD31+ and podoplanin+ cells from hypertensive and normotensive mice. Sequencing of these cells revealed three distinct cell types (LECs, myeloid immune cells, and an unusual third population we dubbed multipotent nephron-associated support cells) with unique expression profiles.

2024-05-14 | GSE236410 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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