Abdominal Aortic Aneurysm in the ApoE Knockout Mouse: Time Course of Control vs. Angiotensin II
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE17901 | GEO | 2009/10/01
SECONDARY ACCESSION(S): PRJNA120089
REPOSITORIES: GEO
Similar Datasets
Project description:Transcriptional profiling of suprarenal aorta from ApoE-/- mice (12-14 weeks old, C57BL/6J background) treated by subcutaneous pump with angiotensin II or saline for 7d, 14d and 28d. Includes Ang II-treated samples at 7d found to have dissected aneurysms. Goal was to examine gene expression in developing AAA in this model over time. Experiment Overall Design: Two condition experiment, one suprarenal aorta per array. Saline vs. angiotensin II at 3 time points, with inclusion of 3 Ang II-treated dissected. Total 35 arrays: 6 saline 7d, 6 saline 14d, 5 saline 28d, 4 Ang II 7d, 5 Ang II 14d, 6 Ang II 28d, 3 Ang II-dissected 7d.
2009-10-09 | E-GEOD-17901 | biostudies-arrayexpress
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: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:Myocardin (Myocd) plays an important role in the maintenance and homeostasis of the vasculature. The loss of Myocd results in vascular smooth muscle cell (VSMC) phenotypic transition and thoracic aortic aneurysms and dissections (TAADs) by downregulating VSMC contractile genes. VSMC phenotypic transition plays a key role in the formation of abdominal aortic aneurysms and dissections (AAADs). However, little is known about the role of Myocd in AAAD. The effect of Myocd on AAA formation was proven in an angiotensin II (Ang II)-induced AAD model. Myocd overexpression or knockdown was achieved by the injection of the corresponding adeno-associated virus serotype 9 (AAV9) through the tail vein. The knockdown of Myocd in C57BL/6J mice treated with angiotensin II promoted the formation of AAAD, as demonstrated by increases in the maximal aortic diameter, vascular inflammation and elastin degradation relative to the control group, while Myocd-overexpressing ApoE-/- mice infused with Ang II were less likely to develop AAAD. Mechanistically, Myocd deficiency significantly repressed VSMC marker gene expression. In addition, qPCR results showed that Myocd knockdown promoted the expression of lncRNAs, which showed increased levels in human AAD tissues. Our results indicated the pivotal role of Myocd in protecting against AAAD formation.
2024-10-25 | GSE180990 | GEO
Project description:Abdominal aortic aneurysm (AAA) is one of the most common fatal macrovascular diseases worldwide which generates huge economic burdens on humanity. Regretfully, the pathogenesis of AAA is still not well clarified. In our study, 10×single-cell sequencing revealed that endothelial cells (ECs) dysfunction and endothelial-mesenchymal transition (EndoMT) appeared in progress of angiotensin (Ang)-II induced AAA. Three different types of ECs, including Mature ECs, EndoMT ECs and Injury & inflammation ECs successively appeared during the progression of AAA. Compared with Mature ECs, EndoMT ECs and Injury & inflammation ECs had stronger extracellular matrix synthesis function and lower metabolic level. Transcription factor analysis revealed that interferon regulatory factor 6 (Irf6) and homeobox A9 (Hoxa9) may be the critical regulons in Injury & inflammation ECs. According pseudotime trajectory and KEGG enrichment analysis, we speculated bone morphogenetic protein 4 (BMP4) regulated EndoMT, thus participating in Ang II-induced AAA. Our study represented BMP4 promotes phenotypic transition, cell migration and invasion of ECs by PI3K/AKT/mTOR pathways in vitro. Protein-protein interaction (PPI) analysis and co-immunoprecipitation (Co-IP) revealed that biglycan (BGN), a kind of small leucine-rich proteoglycan, directly combined with BMP4, which enhanced conversion degree of EndoMT. BMP4 reprogrammed ECs from anti-inflammatory to proinflammatory phenotype, which eventually led to AAA.
2024-07-01 | GSE231306 | GEO
Project description:We report the transcriptomic analysis of RNA-seq of aortas isolated from ApoE-/- mice exposed to Ang II or PBS to uncover the mechanisms underlying the undefined role ripk3 in AAA
2020-08-04 | GSE141726 | GEO
Project description:Analysis of differential gene expression for rutured vs stable abdominal aortic aneurysms (AAA) and for intermediate size (≤55mm) vs large (>70mm) AAA.
2018-02-27 | GSE98278 | GEO
Project description:Endothelial-enriched total RNAs were obtained from the suprarenal region of the abdominal aorta which is the murine AAA prone area in AngII-infused C57BL/6 mice.
2014-07-01 | GSE54943 | GEO
Project description:Aims Abdominal aortic aneurysm (AAA) is a complex aortic disease define by a dilatation of the infrarenal aorta and the most common form of aneurysm in humans. Whereas inflammation contribute to AAA development, quenching vascular inflammation using classical pharmacological approaches or inhibiting the immune system does not influence the progression of AAA in humans indicating the lack of a complete picture on the molecular events that drive this aortopathy. This study was designed to comprehend the earliest molecular indicators, aiming to pinpoint a biological target associated with the latter. Methods and results Using ApoE-deficient mice fed with a standard diet and infused with Angiotensin II (Ang II), we conducted bulk RNA-sequencing analysis on suprarenal (SRA) regions obtained from both unchallenged and challenged WT mice, specifically examining responses 24 hours after Ang II infusion to capture the initial phases of aortic stress response. We further created a unique model of hyperlipidemic mice in which the expression of IKK can be conditionally (via tamoxifen injection) suppressed in vascular SMCs (CreERT2 under the control of the Acta2 promoter). The development of AAA was evaluated using in situ examination and quantified using RT-qPCR, immunohistochemistry and fluorescence microscopy. Cultured vascular SMC were exposed to the selective IKK inhibitor MLN120b and the expression levels of phenotypic markers KLF4, -Catenin and CTGF were addressed using cellular extracts and immunoblot analysis. Results RNASeq data support the presence of early anabolic events in SRA regions detailing activation of the mTORC1 pathway, which paralleled cellular processes including mitochondria, ribosome and sterol biosynthesis and the Unfolded Protein Response (UPR). Conditional deletion of the Ikbkb gene in vascular SMCs significantly reduces the incidence of SRA lesions as well as the rate of aneurysm ruptures in animals exposed to Ang II. In situ analysis further demonstrated that the protection conferred by the lack of IKK expression in vascular SMC is associated with reduced inflammatory response, the preservation of the contractile over the degradative vascular SMC phenotypes and the absence of anabolic and fibrotic signatures. Conclusion Our data not only reinforce the major roles play by vascular SMC in the rapid adaptation leading to the deleterious remodeling of the vascular wall and aortic lesions but also support a paradigm aiming at repositioning the efforts focusing on anabolic rather than inflammatory events.
2025-05-28 | GSE265897 | GEO
Project description:Objective: Angiotensin-II (Ang-II) drives pathological vascular wall remodeling in hypertension and abdominal aortic aneurysm (AAA). Previous studies showed that the phosphatase activity of calcineurin (Cn) mediates Ang-II-induced AAA, but the cell type involved in the action of Cn in AAA formation remained unknown. Methods: Smooth muscle cell (SMC)-specific and endothelial cell (EC)-specific Cn-deficient mice (SM-Cn-/- and EC-Cn-/- mice, respectively) were created and assessed for Ang-II-induced AAA formation and hypertension vs controls. Osmotic minipumps were used to administer Ang-II and cyclosporine A (CsA), a pharmaceutical Cn inhibitor. AAA formation and hypertension were monitored by ultrasonography, arterial blood pressure monitoring, and histological analysis. Deep RNA sequencing was used to identify the Ang-II-regulated transcriptome sensitive to Cn deletion or pharmacological inhibition. Arterial and SMC contractility were also assessed. Results: Cn expressed in SMCs, but not ECs, was required for Ang-II-induced AAA. SMC Cn also played an unexpected structural role in the early onset and maintenance of Ang-II-induced hypertension independently of Cn phosphatase activity. Nearly 90% of the genes regulated by Ang-II in the aorta required Cn expression in SMCs. Cn orchestrated, independently of its enzymatic activity, the induction by Ang-II of a gene expression program closely related to SMC contractility and hypertension. Cn deletion in SMCs, but not its pharmacological inhibition, impaired the regulation of arterial contractility. Among the genes whose regulation by Ang-II required Cn expression but not its phosphatase activity, Serpine1 was critical for Ang-II-induced hypertension. Indeed, pharmacological inhibition of PAI-1, the protein encoded by Serpine1, impaired SMCs contractility and regressed hypertension. Conclusions: Whereas the phosphatase activity of Cn mediates Ang-II-induced AAA, a phosphatase-independent action of SMC Cn underlies blood pressure regulation by orchestrating a gene expression program closely related to contractility regulation and hypertension.
2025-04-21 | GSE255061 | GEO