Single cell RNA sequencing for CD34 lineage cells from normal and Angiotensin Ⅱ-induced abdominal aneurysmal aorta
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE260887 | GEO | 2025/02/26
REPOSITORIES: GEO
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Project description:Aortic aneurysm is a life-threatening disease resulted from progressive dilatation of the aorta and weakness of the blood vessel walls . While the two diseases share several etiological similarities, there are also significant differences in population prevalence rate, genetic patterns and susceptibility genes. However, both TAAs and AAAs are complex, multifactorial and highly heterogeneous diseases, which greatly restricts our better knowledge of the two diseases. An improved knowledge of the cellular mechanism networks that trigger the development and succeeding expansion of aneurysms is critical to discovering innovative therapeutic targets.
2023-02-01 | GSE221789 | GEO
Project description:Aortic aneurysms is increasing as the human population ages. Pathological oxidative stress is implicated in development of aortic aneurysms. We pursued a chemogenetic approach to create an animal model of aortic aneurysm formation using a transgenic mouse line DAAO-TGTie2 that expresses yeast D-amino acid oxidase (DAAO) under control of the endothelial Tie2 promoter. In DAAO-TGTie2 mice, DAAO generates the reactive oxygen species hydrogen peroxide (H2O2) in endothelial cells only when provided with D-amino acids. When DAAO-TGTie2 mice are chronically fed D-alanine, the animals become hypertensive and develop abdominal but not thoracic aortic aneurysms. Generation of H2O2 in the endothelium leads to oxidative stress throughout the vascular wall. Proteomic analyses indicate that the oxidant-modulated protein kinase JNK1 is dephosphorylated by the phophoprotein phosphatase DUSP3 in abdominal but not thoracic aorta, causing activation of KLF4-dependent transcriptional pathways that trigger phenotypic switching and aneurysm formation. Pharmacological DUSP3 inhibition completely blocks aneurysm formation caused by chemogenetic oxidative stress. These studies establish that regional differences in oxidant-modulated signaling pathways lead to differential disease progression in discrete vascular beds, and identify DUSP3 as a potential pharmacological target for the treatment of aortic aneurysms.
2025-02-18 | PXD060700 | Pride
Project description:Tumor necrosis factor (TNF) is elevated in human abdominal aortic aneurysms (AAA). Non-selective TNF inhibition has been linked to several severe side effects. Compounds that target the proinflammatory soluble TNF (solTNF) while preserving the immunomodulatory capabilities of transmembrane TNF (tmTNF) may prevent such side effects. We hypothesize that inhibition of solTNF signaling by XPro1595 is just as effective as non-selective TNF inhibition by etanercept (ETN) in preventing AAA expansion. The effect of XPro1595 and ETN was examined in porcine pancreatic elastase (PPE) induced AAA mice and findings of XPro1595 was confirmed in Angiotensin II (AngII) induced AAA in hyperlipidemic apolipoprotein E (Apoe) -/- mice. XPro1595 treatment significantly reduced AAA expansion in both models, while a similar trend (p=0.06) was observed in ETN-treated mice using the PPE model. In the PPE aneurysm wall, elastin integrity scores were significantly improved in the XPro1595 group. In the aneurysms, mean TNFR1wasreduced no-significantly (p=0.07) by 50% non-significant after TNF inhibition, but the cellular location in murine AAAs were unaffected and like the localization in human AAAs. Systemic TNF levels were elevated in XPro1595-treated mice, while systemic IL-10 levels were significantly increased after ETN-treatment, while in AngII induced AAA mice systemic TNF and IL5 levels were elevated after XPro1595 treatment. In early AAA development, proteomic analyses revealed that components of the fibrinogen complex were elevated while prostaglandin E2 synthase was down regulated by Xpro1595 (unadjusted p-values). David’s ontology analyses revealed that several pathways including cell matrix adhesion, extracellular space, fibrinogen complex, blood microparticles and glycoproteins were elevated by XPro1595 treatment. In conclusion, selective inhibition of solTNF reduces aneurysm expansion. This supports targeting solTNF as an attractive treatment option for AAA patients.
2022-10-14 | PXD035178 | Pride
Project description:Objective-Aortic pathologies exhibit sexual dimorphism, with aneurysms in the ascending, thoracic and abdominal aorta (AAA) exhibiting higher prevalence in males. Despite lower incidence of aortic vascular disease in women, aneurysms progress rapidly. Mechanisms for these sex differences are unclear. We defined the role of sex chromosome complement and testosterone in regional development and progression of angiotensin II (AngII)-induced vascular pathologies. Approach and Results-We used transgenic male mice expressing Sry on an autosome to create low density lipoprotein receptor (Ldlr) deficient male mice with an XY or XX sex chromosome complement. Subjects were then sham operated or orcheictomized. Transcriptional profiling on abdominal aortas from XY or XX males demonstrated1746 genes influenced by sex chromosomes, sex hormones, or an interaction. A second cohort of animals was then infused with AngII for 28 days. Diffuse aortic aneurysm pathology developed in XY AngII-infused males, while XX males developed discrete AAAs. Castration reduced all AngII-induced aortic pathologies in XY and XX males. Thoracic aortas from AngII-infused XY males, but not XX males exhibited adventitial thickening. We infused male XY and XX mice with saline or AngII and quantified mRNA abundance of key genes in thoracic versus abdominal aortas. Regional differences in mRNA abundance existed before AngII infusions, which were differentially influenced by AngII between genotypes. Prolonged AngII infusions resulted in AAA aortic wall thickening in XY males with diffuse aortic pathology, while XX males had dilated focal AAAs. Conclusions-An XY sex chromosome complement mediates diffuse aortic pathology, while an XX sex chromosome complement contributes to discrete AngII-induced AAAs.
2018-07-22 | GSE102143 | GEO
Project description:In this study we used microarrays to examine relative genes expression within the aorta of ApoE-/- infused with angiotensin II in relation to aneurysm formation. Infusion of angiotensin II induces aortic dilatation particularly of the suprarenal aorta in ApoE-/- mice. Based on studies carried out in our and other laboratories the response to angiotensin II is variable, with some mice developing large aneurysms but other animals appearing resistant to aneurysm formation with aortic diameters similar to that of saline controls. We compared RNA expression from whole aortas of 17 week old male ApoE-/- mice exposed to angiotensin II (1.44 µg/kg/min) for 4 weeks where there was clear evidence of aortic aneurysm formation (n=5) with that of mice failing to develop aneurysms (n=7) and those exposed to saline infusion (n=6). AAA was defined as diameter of suprarenal aorta greated than 1.5mm measured on photographs of aortas at necroscopy. Keywords: Disease state analysis 18 samples analysed, AAA (n=5), no AAA (n=7), saline (n=6). AAA - abdominal aortic aneurysm
2010-06-24 | E-GEOD-12591 | biostudies-arrayexpress
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
Project description:Inflammation and elastin degradation are key hallmarks in the pathogenesis of abdominal aortic aneurysms (AAA). It has been acknowledged that activation of alpha7 nicotinic acetylcholine receptors (α7nAChRs) attenuates inflammation, termed the cholinergic anti-inflammatory pathway (CAP). Thus, we hypothesized that low-dose nicotine, an α7nAChR agonist, impairs the progression of AAAs in rats by activating the CAP. Male Sprague-Dawley rats underwent surgical AAA induction with intraluminal elastase infusion. We compared vehicle rats with rats treated with nicotine (1.25 mg/kg/day) and the aneurysm progression was monitored by weekly ultrasound images for 28 days. Nicotine significantly promoted AAA progression after 28 days of treatment (p=0.031). Additionally, gelatin zymography demonstrated that nicotine significantly reduced pro-matrix metalloprotease (pro-MMP) 2(p=0.029) and MMP9(p=0.030) activity in aneurysmal tissue. No significant difference was found in elastin content or the score of elastin degradation between the groups. Neither infiltrating neutrophils nor macrophages, nor aneurysmal messenger RNA (mRNA) levels of pro- or anti-inflammatory cytokines differed between the vehicle and nicotine group. Finally, no difference in mRNA levels of markers for antioxidative stress or vascular smooth muscle cells contractile phenotype was observed. However, proteomics analyses of non-aneurysmal abdominal aortas revealed that nicotine decreased proteins in the ontology terms inflammation and reactive oxygen species and in contradiction to augmented AAAs. In conclusion, treatment with the given nicotine dose augmented AAA progression in this rat model.
2023-07-20 | PXD040414 | Pride
Project description:Wall shear stress (WSS) is proposed to influence intracranial aneurysm growth and rupture. Physiological WSS in cerebral arteries is estimated around 20-30 dynes/cm2. The WSS typically observed in human IAs is close to 2 dynes/cm2 for wide-neck aneurysms with a slow recirculating flow and >70 dynes/cm2 in aneurysms with impinging “jet flow”. In this study, we investigated the effects of aneurysmal low and supra-high WSS on endothelial cells.
2021-11-04 | GSE173928 | GEO
Project description:In this study we used microarrays to examine relative genes expression within the aorta of ApoE-/- infused with angiotensin II in relation to aneurysm formation. Infusion of angiotensin II induces aortic dilatation particularly of the suprarenal aorta in ApoE-/- mice. Based on studies carried out in our and other laboratories the response to angiotensin II is variable, with some mice developing large aneurysms but other animals appearing resistant to aneurysm formation with aortic diameters similar to that of saline controls. We compared RNA expression from whole aortas of 17 week old male ApoE-/- mice exposed to angiotensin II (1.44 µg/kg/min) for 4 weeks where there was clear evidence of aortic aneurysm formation (n=5) with that of mice failing to develop aneurysms (n=7) and those exposed to saline infusion (n=6). AAA was defined as diameter of suprarenal aorta greated than 1.5mm measured on photographs of aortas at necroscopy. Keywords: Disease state analysis
2009-08-26 | GSE12591 | GEO
Project description:Dissecting abdominal aortic aneurysm (AAA) is a life-threatening condition characterized by medial layer degeneration of the abdominal aorta. Complex, complicated, and extremely heterogeneous diseases like dissecting AAAs severely limit our ability to understand it. A thorough understanding of cell types and signaling pathways associated with the initiation and progression of dissecting AAA is essential for the development of medical therapy. Single-cell RNA sequencing (scRNA-seq) was performed on the abdominal aortas from ApoE-/- mice at days 28 post-Angiotensin II-induced mouse dissecting AAAs. According to the Angiotensin II-induced dissecting AAA model described in this study, alterations in cellular subpopulations, fractions, and transcriptome profiles are present.
2024-09-19 | GSE239620 | GEO