Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA280736 | ENA |
REPOSITORIES: ENA
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Project description:Fibulin-4 plays an essential role in elastic fiber formation, though it's exact function is unclear. Mice lacking the fibulin-4 gene develop cutis laxa with thoracic aortic aneurysms and have narrowed descending aortic diamaters, dying shortly after birth. Another model that disrupt elastic fiber formation, elastin gene knockeds, are also perinatally lethal and have narrowed descending aortas but do not develop thoracic aneurysms. We hypothesized that there may be altered gene expression to explain the altered anatomy based on aortic tissue location we observed, which may provide therapeutic target(s) Ascending and descending aortas of p0 mouse pups were dissected, pooled in groups of eight, and homogenized to isolate RNA and we used microarrays on the pooled samples to identify genes that had expression significantly changed.
2015-04-10 | E-GEOD-67707 | biostudies-arrayexpress
Project description:Fibulin-4 plays an essential role in elastic fiber formation, though it's exact function is unclear. Mice lacking the fibulin-4 gene develop cutis laxa with thoracic aortic aneurysms and have narrowed descending aortic diamaters, dying shortly after birth. Another model that disrupt elastic fiber formation, elastin gene knockeds, are also perinatally lethal and have narrowed descending aortas but do not develop thoracic aneurysms. We hypothesized that there may be altered gene expression to explain the altered anatomy based on aortic tissue location we observed, which may provide therapeutic target(s)
2015-04-10 | GSE67707 | GEO
Project description:The purpose of this study was to determine whether lysyl oxidase inhibition using β-aminopropionitrile (BAPN) induced region-specific aortopathies in mice. The effects of BAPN were first characterized with regard to dose, strain, age, and sex. Subsequently, BAPN was administered to young male C57BL/6J mice. BAPN-induced aortic rupture predominantly occured or originated in the descending thoracic aorta. For mice surviving 12 weeks of BAPN administration, profound dilatation was consistently observed in the ascending region, while relatively sporadic in the descending thoracic region. Pathological features were distinct between the ascending and descending thoracic regions. Aortic pathology in the ascending region was characterized by luminal dilatation and elastic fiber disruption throughout the media. The descending thoracic region frequently had dissection with false lumen formation, macrophage infiltration, collagen deposition, and remodeling of the media and adventitia. Cells surrounding the false lumen were predominantly positive for α-smooth muscle actin. To investigate the molecular basis of the regional heterogeneity, ascending and descending thoracic aortas were harvested after one week of BAPN administration prior to the appearance of overt pathology. BAPN compromised contractile properties in both regions equivalently, while RNA sequencing demonstrated that BAPN altered transcriptomes related to extracellular matrix and cell division differentially between the two regions. In conclusion, BAPN-induced pathologies show distinct, heterogeneous features within and between ascending and descending aortic regions in young mice.
2023-09-30 | GSE241968 | GEO
Project description:Comparisons of canine arterial gene expression between control and untreated MPS animals were conducted with a canine-specific microarray covering 43,803 probes (Agilent G2519F 4x44k, Santa Clara, CA), for a total of four comparison groups: MPS ascending aorta vs. control ascending aorta, MPS descending aorta vs. control descending aorta, MPS carotid artery vs. control carotid artery, and finally pooled MPS artery (ascending aorta, descending aorta, carotid artery) vs. pooled control artery. Each comparison used four pairs of MPS vs corresponding age- and gender- matched animals to produce four biologic replicates.
2016-03-05 | GSE78889 | GEO
Project description:Background: Individuals with Loeys-Dietz syndrome 3 (LDS3) are at risk for thoracic aortic dissection even if their aortas are not substantially dilated. A pathogenic variant of SMAD3 is a genetic trigger, but the cellular programs that underlie the heightened aortic risk remain poorly understood. Methods: We ascertained the cardiovascular profile of 57 individuals in a four-generation family with a missense variant in SMAD3 (p.Arg287Gln). Aortic medial architectures were quantified from aortas harvested during thoracic aortic replacement surgery, with 2D and 3D profiling of the elastin-microfibril network. TGF-beta-dependent regulatory networks were investigated by whole-genome RNA sequencing of ascending aortic smooth muscle cells (SMCs) and bioinformatics-informed chromatin immunoprecipitation. Results: Cardiovascular phenotypes of family members harboring the SMAD3 variant included thoracic aortopathy, peripheral artery aneurysms and tortuosity, cerebrovascular disease, coronary artery dissections, and mitral valve prolapse. The median age at the first aortic event was 36.5 years. Ascending aortas were less dilated than the aortic root, with relatively intact lamellar structure and SMC content. However, early pathology was evident, with SMCs separated from elastic lamellae by a thin layer of glycosaminoglycans. Confocal reconstructions revealed that elastic fibers were poorly decorated by microfibrils, with reduced fibrillin-1, fibrillin-2, microfibril associated glycoprotein-2, fibulin-1 and fibulin-2. RNA sequencing of LDS3 SMCs revealed reduced expression of microfibrils. Furthermore, Paired Related Homeobox 2 (PRRX2) was found to be down-regulated in LDS3 SMCs in culture and in situ, occupy gene promoter sites for all five microfibrils, and mediate their expression in SMCs. SMAD3 overexpression rescued both PRRX2 and microfibril expression. Conclusions: These findings identify SMCs delaminating from unsheathed elastic fibers as an incipient pathological program in LDS3 aortas. They also uncover a SMAD3-PRRX2-microfibril axis that, being perturbed, could explain this disconnection phenomenon and contribute to risk.
2026-07-29 | GSE330831 | GEO
Project description:Mucopolysaccharidosis VII (MPS VII) is due to mutations within the gene encoding the lysosomal enzyme beta-glucuronidase, and results in the accumulation of glycosaminoglycans. MPS VII causes aortic dilatation and elastin fragmentation. In this study we performed microarray analysis of ascending aortas from normal and MPS VII mice, trying to find out possible genes responsible for the phenotype observed. In addition, during our breeding strategy, we noticed that some MPS VII mice had less dilated aortas, and we proposed that an yet-unidentified gene could be responsible for the difference observed. We therefore included in the analysis two MPS VII mice with aortas that were not dilated. Total RNA extracted from ascending aortas from 3 Normal mice, 3 MPS VII mice with dilated aortas and 2 MPS VII mice with aortas that were not dilated.
2011-10-09 | E-GEOD-30657 | biostudies-arrayexpress
Project description:We have shown that vascular SMCs, fibroblasts, and endothelial cells have transcriptional and epigenomic features that are distinct to vascular site. Further, TF motif accessibility analysis in fibroblasts reveals an increased accessibility of AP1, and SMAD2:3:4, and TCF21 motifs in the ascending fibroblast population compared to carotid and descending fibroblasts, with further gene regulatory network analysis suggesting distinct regulatory TF module activity in ascending fibroblasts highlighting master regulator of fibroblast activation Meox1. This differential chromatin accessibility would suggest the potential for heightened biological response to TGFb in ascending fibroblasts. To evaluate the functional effect of this differential chromatin accessibility and to identify if differential gene expression is retained following removal from vascular site flow conditions, we isolated and cultured primary adventitial fibroblasts from healthy 14 week old C57BL/6 mice from the ascending and descending aorta and stimulated them with control or TGFb (10ng/mL, 48hrs) and performed bulk RNA sequencing (n = 3 per condition).
2025-07-29 | GSE296074 | GEO
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
Project description:Enlargement or aneurysm of the aorta predisposes to dissection, an important cause of sudden death. We trained a deep learning model to evaluate the dimensions of the ascending and descending thoracic aorta in 4.6 million cardiac magnetic resonance images from the UK Biobank. We then conducted genome-wide association studies in 39,688 individuals, revealing 82 loci associated with ascending and 47 with descending thoracic aortic diameter, of which 14 loci overlapped. Transcriptome-wide analyses, rare-variant burden tests, and human aortic single nucleus RNA sequencing prioritized genes including SVIL, which was strongly associated with descending aortic diameter. A polygenic score for ascending aortic diameter was associated with thoracic aortic aneurysm in 385,621 UK Biobank participants (HR = 1.43 per SD; CI 1.32-1.54; P = 3.3·10-20). Our results illustrate the potential for rapidly defining quantitative traits with deep learning, an approach that can be broadly applied to biomedical images.
2021-01-30 | GSE165824 | GEO
Project description:Mucosal pinch biopsies from ascending, transverse, descending colon and rectum were obtained from ulcerative colitis (UC), primary sclerosing cholangitis concomitant with colitis (PSC-UC) and healthy control patients during routine endoscopies and cryopreserved. Biopsies were then thawed, digested and subjected to 5' single-cell RNA sequencing with V(D)J TCR analysis.
2026-06-29 | E-MTAB-17148 | biostudies-arrayexpress