Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Increased vascular smooth muscle cell senescence in aneurysmal Fibulin-4 mutant mice

ABSTRACT: Increased vascular smooth muscle cell senescence in aneurysmal Fibulin-4 mutant mice

PROVIDER: PRJNA1104590 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

Increased vascular smooth muscle cell senescence in aneurysmal Fibulin-4 mutant mice

Project description:Aortic aneurysms are dilations of the aorta that can rupture when left untreated. We used aneurysmal Fibulin-4R/R to further unravel the underlying mechanisms of aneurysm formation. RNA sequencing of 3-month-old Fibulin-4R/R aortas revealed significant upregulation of senescence-associated secretory phenotype (SASP) factors and key senescence factors, indicating involvement of senescence. Analysis of aorta histology and of vascular smooth muscle cells (VSMCs) in vitro confirmed the senescent phenotype of Fibulin-4R/R VSMCs by revealing increased SA-β-gal, p21 and p16 staining, increased IL-6 secretion, increased presence of DNA damage foci and increased nuclei size. Additionally, we found that p21 luminescence was increased in the dilated aorta of Fibulin-4R/R|p21-Luciferase mice. Our studies identify a cellular aging cascade in Fibulin-4 aneurysmal disease, by revealing that Fibulin-4R/R aortic VSMCs have a pronounced SASP and a senescent phenotype that may underlie aortic wall degeneration. Additionally, we demonstrated the therapeutic effect of JAK/STAT and TGF-β pathway inhibition as well as senolytic treatment on Fibulin-4R/R VSMCs in vitro. These findings can contribute to improved therapeutic options for aneurysmal disease aimed at reducing senescent cells.

2024-04-30 | GSE265869 | GEO

Transcription profiling of aorta from mice underexpressing Fibulin-4 to investigate its role in elastic fibre assembly and cardio-vasuclar disease

Project description:Extracellular elastic fibres apply structure and mechanical elasticity to organs such as large arteries, lungs and skin 1. Elastic fibres are assembled through polymerization of tropoelastin monomers and loss of elastin is associated with aneurysmal degeneration of the aorta 2. The Fibulins are a six-member protein family hypothesized to function as intermolecular bridges that stabilize the organization of extracellular matrix structures such as elastic fibres and basement membranes 3. Fibulin-4 is found in the medial layers of arteries and moderately expressed in heart valves 4. To examine a potential role of Fibulin-4 in elastic fibre assembly and cardio-vascular disease we generated a mouse model underexpressing Fibulin-4. To get insight into the underlying molecular pathways involved in aneurysm formation, we determined the aorta transcriptome of Fibulin-4R/R animals and identified biological processes that were significantly overrepresented including apoptosis and cell death as well as several novel gene targets implicated in the response to aortic failure. We conclude that decreased Fibulin-4 expression causes aberrant composition of the elastin layers in the aorta and valvular leaflets, resulting in aortic aneurysms and heart abnormalities.

2007-01-01 | E-MEXP-840 | biostudies-arrayexpress

Vascular smooth muscle cell senescence instigates thoracic aortic aneurysm

Project description:In this study, we identified various cell clusters in human normal/sporadic TAA ascending aorta samples by single-cell RNA sequencing (scRNA-seq), and discovered the senescent vascular smooth muscle cells (VSMCs) significantly increased in TAA samples. Then we explored the molecular basis of TAA progression, and recognized the key regulators and pathways involved in the TAA progression regulation.

2023-12-01 | GSE143921 | GEO

Human vascular smooth muscle cells undergoing cell senescence

Project description:Vascular smooth muscle cells (VSMCs) undergo cell senescence in a number of diseases, both due to stress and loss of replication. Here we have cultured human VSMCs to replicative senescence, or induced stress-induced premature senescence (SIPS), and compared their transcriptome with cells treated with doxorubicin for 1d or control cells

2021-05-18 | GSE171663 | GEO

Genome-wide identification of transcriptional targets for H3K23ac, H3K27ac, and H4K5ac in vascular smooth muscle cells of aneurysmal aortas [CUT&Tag]

Project description:In this study, we found that H3K23ac, H3K27ac, and H4K5ac level are elevated in VSMCs of aneurysmal aortas. To further explore the potential functional significance of H3K23ac, H3K27ac, and H4K5ac in aortic aneurysm, we performed genome-wide cleavage under targets and tagmentation (CUT&Tag) analysis to identify candidate genes regulated by H3K23ac, H3K27ac, or H4K5ac in rat VSMC. Following CUT&Tag, H3K23ac, H3K27ac, or H4K5ac-associated DNAs were amplified using non-biased conditions, labeled, and sequenced with Illumina NovaSeq 150PE.

2024-10-28 | GSE277724 | GEO

Effect of fibulin-3 knockdown on malignant mesothelioma cells

Project description:Whole transcriptome comparison of mesothelioma cells transfected with control vs Fibulin-3 (EFEMP1) siRNAs. Mesothelioma cells H-226 (ATCC) and H-2595 (Harvey Pass, New York University) were transfected with two fibulin-3 or control siRNAs and collected 48h after transfection. Gene expression was quantified by RNAseq using standard procedures. The results suggest that downregulation of fibulin-3 negatively affects a PI3K/AKT-dependent gene signature involved in cell growth, adhesion, and association with the extracellular matrix.

2020-12-15 | GSE133933 | GEO

MERSCOPE profiling of non-aneurysmal and aneurysmal human ascending aorta

Project description:Single-molecule level spatial distribution of MERFISH (Multiplexed error-robust fluorescence in situ hybridization) probes targeting 140 genes were analyzed on two control (non-aneurysmal) samples and three TAA samples with Thoracic aortic aneurysm (TAA).

2023-10-14 | GSE241870 | GEO

Altered microRNA expression: Control vs. Intracranial Aneurysmal Tissues

Project description:High throughput miRNA microarray screening approach, we compared the miRNA expression pattern in ruptured aneurysm tissues obtained during surgery from patients with aneurysmal subarachnoid hemorrhage (aSAH) with control tissues. Aim was to determine miRNA signature in aneurysmal tissues.

2020-11-21 | GSE161870 | GEO

MERSCOPE profiling of non-aneurysmal and aneurysmal human ascending aorta

Project description:MERSCOPE profiling of non-aneurysmal and aneurysmal human ascending aorta

| PRJNA1010377 | ENA

Human vascular smooth muscle cells undergoing cell senescence

Project description:Human vascular smooth muscle cells undergoing cell senescence

| PRJNA720431 | ENA