Single cell transcriptomics of mouse abdominal aortic aneurysm induced by AngII plus salt [28days]
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE302875 | GEO | 2025/11/18
REPOSITORIES: GEO
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Project description:Abdominal aortic aneurysm (AAA) is a vascular disease with high incidence at present.There is no effective drug treatment. MicroRNAs(miRNAs) play a regulatory role in the occurrence and development of AAA,and miRNA therapy is a promising treatment for AAA. The purpose of this study was to explore the differential expression of miRNAs in abdominal aorta of ApoE-/- AngII-induced abdominal aortic aneurysm mices. We used miRNA array to analyze miRNA differences in abdominal aorta between mices with ApoE-/- AngII-induced abdominal aortic aneurysm and ApoE-/-.
2025-10-29 | GSE280216 | GEO
Project description: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.
2023-12-07 | GSE183464 | GEO
Project description:The present study was undertaken to test the hypothesis that EPO may promote the formation of abdominal aortic aneurysm (AAA) via angiogenesis and inflammatory response. We injected EPO in different doses to Apoe-/- and WT mice, used EPO mAb in Apoe-/- mice with AngII stimulation, injected a selective activator of the heterodimer receptors of EPO into Apoe-/- and WT mice, and created CRISPR-mediated EPOR knockout (Epor+/-Apoe-/-) mice. In addition, we measured serum EPO concentration in healthy controls and patients with AAA, and performed a series of in vitro and ex vivo experiments in ECs, SMCs, and macrophages. Our results showed that EPO dose-dependently promoted the formation of AAA, with a high occurrence rate in both Apoe-/- and WT mice, and there was a close relationship between serum concentration of EPO and the incidence of AAA in Apoe-/- and WT mice receiving AngII or EPO treatment. The major mechanism involved angiogenesis, inflammatory response, SMCs apoptosis and collagen degradation via EPO-EPOR-JAK2/STAT5 signaling pathway in vascular cells. Administration of EPO neutralizing antibody suppressed AngII-induced AAA formation, and the incidence of AAA was dramatically reduced in Epor+/-Apoe-/- versus Apoe-/- mice after AngII infusion. In addition, serum EPO concentration was substantially higher in patients with AAA than in healthy subjects and correlated with the size of AAA in patients. In conclusion, EPO promotes the formation of AAA in both Apoe-/- and WT mice likely via enhanced angiogenesis, inflammation, SMCs apoptosis and collagen degradation, and EPO/EPOR signaling is essential for AngII-induced and possibly human AAA.
2021-05-18 | GSE174556 | GEO
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
Project description:Background: Perivascular adipose tissue (PVAT) is a key regulator of vascular dysfunction. Impairment of PVAT phenotypic plasticity with aging may play a role in vascular pathology including abdominal aortic aneurysms (AAA). Yet, the mechanisms underlying PVAT plasticity in aneurysm pathogenesis remain elusive. Methods: Single-cell RNA sequencing (scRNA-seq) was performed on perivascular stromal cells (PVSCs) from young (2-3-month-old) and aged (18-20-month-old) mice. The expression of peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) was measured in PVAT of aged mice and human aneurysm samples. Loss- and gain-of-function approaches were employed to investigate the role of SM22α-lineage PVSCs-derived PGC-1α in aneurysm development. Molecular mechanisms were explored through transcriptome and functional studies in young and aged mice, SM22αCre; Rosa26RFP/+; PGC1αf/f and SM22αCre; Rosa26RFP/+ mice with angiotensin II (AngII)- and DOCA/salt- induced AAA models. Results: SM22α+ cells accumulated in PVAT of angiotensin II-treated aged mice and patients with aortic aneurysms. scRNA-seq analysis revealed that aging disrupted the differentiation potential of SM22α-lineage PVSCs and led to reduced PGC-1α level. PGC1α downregulation in PVAT was observed in both mice AAA models and human aneurysm lesions. In mice with SM22α-driven PGC-1α-deletion AngII induced AAA formation was accompanied by PVSC-to-myofibroblast differentiation. in vitro PGC1α-knockdown suppressed nuclear YAP signaling, reducing adipocyte differentiation, while increasing MMP2-secreting myofibroblasts. Furthermore, PGC-1α overexpression in aged mice or administration of the YAP signaling inhibitor Verteporfin in SM22αCre; Rosa26RFP/+; PGC1αf/f mice restored PVAT function and conferred protection against aneurysm formation. Lastly, we employed the radiomics analysis to non-invasively evaluate PVAT in the context of AAA severity in humans. Conclusions: PGC-1α deficiency in SM22α-lineage stromal cells disrupts the balance between adipogenic and myofibrogenic differentiation through regulating the YAP signaling, ultimately promoting aneurysm development. Radiomics assessment may present a promising noninvasive approach for PVAT evaluation in aneurysms, offering valuable potential for clinical research.
2025-05-09 | GSE293558 | GEO
Project description:An abdominal aortic aneurysm (AAA) is a pathological dilatation of the aortic wall and it is a life-threatening disease due to the risk of rupture. Currently, surgical intervention remains the only definitive treatment recommended for large or rapidly expanding aneurysms. No pharmacological therapy is currently available to prevent AAA progression, as no drug has been proven effective. Diabetes is a major risk factor for cardiovascular disease in general. However, many studies over the last decade show that type 2 diabetes patients have a lower incidence of AAA and a slower aneurysm growth rate, which has been correlated with metformin use. We performed a proteomics analysis on resected aortic tissue from controls, non-diabetic (ND) and diabetic (D) AAA patients.
2025-09-29 | PXD067859 | Pride
Project description:Background: Abdominal Aortic Aneurysm (AAA) is a catastrophic disease with little effective therapy, likely due to the limited understanding of the mechanisms underlying AAA development and progression. Activating transcription factor (ATF) 3 has been increasingly recognized as a key regulator of cardiovascular diseases. However, the role of ATF3 in AAA development and progression remains elusive. Methods: Genome-wide RNA sequencing analysis was performed on the aorta isolated from saline or Ang II-induced AAA mice, and ATF3 was identified as the potential key gene for AAA development. To examine the role of ATF3 in AAA development, vascular smooth muscle cell (VSMC)-specific ATF3 knockdown or overexpressed mice by recombinant adeno-associated virus serotype 9 (rAAV9) vectors carrying ATF3, or shRNA-ATF3 with SM22α promoter were used in AngII (angiotensin II) induced AAA mice. In human and murine VSMCs, gain or loss of function experiments were performed to investigate the role of ATF3 in VSMC proliferation and apoptosis. Results: In both AngII-induced AAA mice and AAA patients, the expression of ATF3 was reduced in aneurysm tissues but increased in aortic lesion tissues. The deficiency of ATF3 in VSMC promoted AAA formation in AngII-induced AAA mice. PDGFRB was identified as the target of ATF3, which mediated VSMC proliferation in response to TNF-alpha at the early stage of AAA. ATF3 suppressed the mitochondria-dependent apoptosis at the advanced stage by upregulating its direct target BCL2. Our ChIP results also demonstrated that the recruitment of NFκB1 and P300/BAF/H3K27ac complex to the ATF3 promoter induces ATF3 transcription via enhancer activation. NFKB1 inhibitor (Andrographolide) inhibits the expression of ATF3 by blocking the recruiters NFKB1 and ATF3-enhancer to the ATF3-promoter region, ultimately leading to AAA development. Conclusions: Our results demonstrate a previously unrecognized role of ATF3 in AAA development and progression, and ATF3 may serve as a novel therapeutic and prognostic marker for AAA.
2024-09-01 | GSE261595 | GEO
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:Difference analysis of microRNAs in abdominal aorta of ApoE-/- AngII-induced abdominal aortic aneurysm mices
| PRJNA1177377 | ENA
Project description:Inflammation is still a crucial factor in the development of abdominal aortic aneurysm (AAA). The CD45+ cell population of elastase-induced murine AAA was deconstructed at the single-cell level using the single-cell RNA (scRNA) transcriptomic technique.
2023-07-18 | GSE237067 | GEO