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RNA-sequencing of abdominal aortic aneurysm (AAA) and control abdominal aorta tissues

ABSTRACT: Abdominal aortic aneurysm (AAA) is a permanent segmental dilatation of the abdominal aorta, contributing to a high mortality once rupture. We performed RNA-sequencing analysis of abdominal aorta tissues from 14 participants, including seven patients with AAA and seven control individuals.

ORGANISM(S): Homo sapiens

PROVIDER: GSE183464 | GEO | 2023/12/07

REPOSITORIES: GEO

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PRDM16 Deficiency in Vascular Smooth Muscle Cells Aggravates Abdominal Aortic Aneurysm

Project description:Abdominal aortic aneurysm (AAA) is usually asymptomatic until life-threatening complications occur, predominantly involving aortic rupture. Currently, no drug-based treatments are available, primarily due to limited understanding of AAA pathogenesis. The transcriptional regulator PR domain–containing protein 16 (PRDM16) is highly expressed in the aorta, but its functions in the aorta are largely unknown. By RNA-seq analysis, we found that vascular smooth muscle cell–specific (VSMC-specific) Prdm16-knockout (Prdm16SMKO) mice already showed extensive changes in the expression of genes associated with extracellular matrix (ECM) remodeling and inflammation in the abdominal aorta under normal housing conditions without any pathological stimuli. Human AAA lesions displayed lower PRDM16 expression. Periadventitial elastase application to the suprarenal region of the abdominal aorta aggravated AAA formation in Prdm16SMKO mice. During AAA development, VSMCs undergo apoptosis because of both intrinsic and environmental changes, including inflammation and ECM remodeling. Prdm16 deficiency promoted inflammation and apoptosis in VSMCs. A disintegrin and metalloproteinase 12 (ADAM12) is a gelatinase that can degrade various ECMs. We found that ADAM12 is a target of transcriptional repression by PRDM16. Adam12 knockdown reversed VSMC apoptosis induced by Prdm16 deficiency. Our study demonstrated that PRDM16 deficiency in VSMCs promoted ADAM12 expression and aggravates AAA formation, which may provide potential targets for AAA treatment.

2023-06-08 | GSE222440 | GEO

Expression profiling of mRNAs and long noncoding RNAs in mouse Abdominal Aortic Aneurysm (AAA)

Project description:mRNA and Long noncoding RNA profiles in the mouse abdominal aorta with AAA and without AAA.

2017-08-01 | GSE63396 | GEO

Single cell transcriptomics of human abdominal aortic aneurysm [scRNA-seq]

Project description:An abdominal aortic aneurysm (AAA) is a pathological widening of the aortic wall characterized by loss of AoSMCs, extracellular matrix degradation and local inflammation. This condition is often asymptomatic until rupture occurs, leading to high morbidity and mortality rates. We conducted single-cell RNA sequencing (scRNA-seq) from AAA patients´s specimens to profile gene expression at single cell level and to gain insight on cell types relevant to disease dynamics.

2023-08-30 | GSE237230 | GEO

Murine Abdominal Aortic Aneurysm, PPE Model: Transcriptional Profiling of Sham vs. AAA at Day 7

Project description:Transcriptional profiling of infrarenal aortic tissue from Male 10-week-old C57BL/6J mice after AAA-induction with porcine pancreatic elastase, compared with sham-operated mice. Includes samples obtained 7 days after aneurysm induction. Goal was to examine gene expression in developing AAA in this model, and compare with miRNA profiling performed using the same tissue. Two condition experiment, one infrarenal aorta per array. Sham vs. PPE at Day 7 post-operatively. Total 10 arrays: 5 sham D7, 5 PPE D7.

2014-08-31 | E-GEOD-51227 | biostudies-arrayexpress

Genome-wide expression profiling of the perivascular adipose tissue in abdominal aortic aneurysm

Project description:Perivascular adipose tissue (PVAT) is thought to play a role in vascular homeostasis and in the pathogenesis of diseases of large vessels, including abdominal aortic aneurysm (AAA). We tested the hypothesis that locally restricted transcriptional profiles characterize PVAT surrounding AAA. Using a genome-wide approach, we investigated the PVAT transcriptome of AAA in 30 patients with either large (≥55 mm) or small (<55 mm) aneurysm diameter. We performed a data adjustment step using the DaMiRseq R/Bioconductor package, to remove the effect of confounders as produced by high-throughput gene expression techniques. We compared PVAT of AAA with PVAT of not-dilated abdominal aorta of each patient to limit the effect of inter-individual variability, using the limma R/Bioconductor package. We found highly consistent differences in PVAT gene expression clearly distinguishing PVAT of AAA from PVAT of not-dilated aorta, which increased in number and magnitude with increasing AAA diameter. These changes did not systemically affect other abdominal adipose depots (omental or subcutaneous fat). We dissected putative mechanisms associated with PVAT involvement in AAA through a functional enrichment network analysis: both innate and adaptive immune-response genes along with genes related to cell-death pathways, metabolic processes of collagen, sphingolipids, aminoglycans and extracellular matrix degradation were strongly overrepresented in PVAT of AAA compared with PVAT of not-dilated aorta. Our results provide support to a possible role of PVAT in AAA pathogenesis and suggest that AAA is an immunologic disease with an underlying autoimmune component. These disease-specific expression signatures could help identifying pharmacological targets for preventing AAA progression.

2018-12-27 | GSE119717 | GEO

Lysyl hydroxylase 1 deficiency exacerbates the alterations of gene transcriptional profile of abdominal aorta in angiotensin II induced abdominal aortic aneurysm

Project description:Lysyl hydroxylase 1 (LH1) plays an important role in hydroxylation of lysyl residuel in Xaa-Lys-Gly. The hydroxylysine residues serve as sites of attachment for carbohydrate units which are essential for the formation of intra- and intermolecular collagen crosslinks. To gain mechanistic insights into the effects of LH1 deficiency on abdominal aortic aneurysm (AAA) formation, a whole transcriptomic analysis of abdominal aorta were performed using RNA-seq. The abdominal aorta of mice for RNA-seq were acquired at day 14 after angiotensin II infusion in order to provide the mechanistic or causal evidence of a direct participatory role of LH1 to the effects of AAA.

2021-08-15 | GSE175683 | GEO

Comparison of infrarenal and suprarenal sections of mouse ApoE-/- abdominal aorta

Project description:The ApoE -/- mice model of abdominal aortic aneurysm (AAA) involves introducing Angiotensin II subcutaneously to 14 week old male mice for 4 weeks by osmotic pump. A significant number of mice will develop aneurysm-like dilations in the suprarenal section of the abdominal aorta (SRA) that have a number of similarities to the human condition and make this a useful model of AAA. The mouse infrarenal aorta is very resistant to aneurysm formation while in humans AAA predominately occurs in the infrarenal section of the aorta (IRA). There have been a number of theories proposed to explain the site selctivity of aneurysm formation in AAA and this mice model. This study was designed to ascertain differences between SRA and IRA that may explain this site selectivity. Keywords: tissue type comparison

2010-05-12 | GSE7006 | GEO

IL-27 receptor signaling regulated stress hematopoiesis drives Abdominal Aortic Aneurysm development

Project description:Abdominal Aortic Aneurysm (AAA) is a prevalent life-threatening disease, where aortic wall degradation is mediated by accumulated immune cells. Though cytokines regulate inflammation within the aorta, their contribution to AAA via distant alterations, particularly in the control of hematopoietic stem cell (HSC) differentiation remains poorly defined. Here we report a pathogenic role for the interleukin-27 receptor (IL-27R) in AAA as genetic ablation of IL-27R protects mice from the disease development, where the mitigation of AAA is associated with a blunted accumulation of myeloid cells in the aorta due to the attenuation of Ang II-induced HSC expansion. The loss of IL-27R engages transcriptional programs that promote HSCs quiescence and suppresses differentiation decreasing mature myeloid cell production and accumulation in the aorta. Our studies illuminate how a prominent vascular disease can be distantly driven by cytokine dependent regulation of bone marrow precursors.

2019-10-14 | GSE129881 | GEO

Identification of potential plasma biomarkers for abdominal aortic aneurysm using tandem mass tag quantitative proteomics

Project description:Plasma biomarkers that identify abdominal aortic aneurysm (AAA) rupture risk would greatly assist in stratifying patients with small aneurysms. Identification of such biomarkers has hitherto been unsuccessful over a range of studies using different methods. The present study used an alternative proteomic approach to find new, potential plasma AAA biomarker candidates. Pre-fractionated plasma samples from twelve patients with AAA and eight matched controls without aneurysm were analyzed by mass spectrometry applying a tandem mass tag (TMT) technique. Eight proteins were differentially regulated in patients compared to controls, including decreased levels of the enzyme bleomycin hydrolase. The down-regulation of this enzyme was confirmed in an extended validation study using an ELISA assay. The TMT-based proteomic approach thus identified novel potential plasma biomarkers for AAA.

2018-10-22 | PXD011309 | Pride

Differential gene expression in human abdominal aortic aneurysm and atherosclerosis

Project description:The aim of this study was to assess the relative gene expression in human AAA and AOD. Genome-wide expression analysis of abdominal aortic aneurysm (AAA) and aortic occlusive disease (AOD) specimens obtained from 20 patients with small AAA (mean maximum aortic diameter=54.3±2.3 mm), 29 patients with large AAA (mean maximum aortic diameter=68.4±14.3 mm), and 9 AOD patients (mean maximum aortic diameter=19.6±2.6 mm). Relative aortic gene expression was compared with that of 10 control aortic specimen of organ donors.

2015-06-30 | E-GEOD-57691 | biostudies-arrayexpress

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