MiRNA analysis in Thoracic Aortic aneurysms
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ABSTRACT:
PROVIDER: PRJNA635645 | ENA |
REPOSITORIES: ENA
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Project description:Thoracic Aortic Aneurysm (TAA) is characterized by the dilation and degradation of the aorta and is fatal if not diagnosed and treated appropriately. There are no specific clinical symptoms, so better knowledge of the physiopathology of TAAs and their underlying genetic mechanisms is needed to improve diagnosis and therapy. MiRNAs regulate gene expression post-transcriptionally and are known to be involved in cerebrovascular disease. The current study aimed to identify differentially expressed miRNAs in patients with TAAs and determine whether their predicted target genes could be associated with this condition. Nanostring assays identified miRNAs in plasma and tissue samples from four TAA patients. RT-PCR validated the expression levels of these miRNAs in a further 22 plasma samples. Three, hsa-miR140-5p, hsa-miR-191-5p and hsa-miR-214-3p showed significant expression level differences between plasma samples collected pre- and post-surgically from each patient. Analyses of the predicted target gene controlled by these miRNAs revealed nine genes whose expression was investigated in the same 22 plasma samples. The gene expression levels were inversely correlated with the expression of their respective miRNAs. From these, CCND2, CRKL, HEY1, MTMR4, NFIA and PPP1CB, showed fold-change differences >1.5 between the two plasma samples. An in-depth literature search and Cytoscape software three genes; MTMR4, NFIA and PPP1CB, showed a possible association with the TGF-β signalling pathway. It is suggested that the three miRNAs detected together with their target genes could play a role in the TGF-β signalling pathway and thus be involved in TAA pathogenesis.
2020-05-29 | GSE151378 | GEO
Project description:Expression data in Abdominal Aortic Aneurysms
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Project description:Patients with bicuspid aortic valve (BAV) have increased risk of thoracic ascending aortic aneurysm (AscAA) and dissection compared to those with a normal tricuspid aortic valve (TAV). The present study was undertaken to evaluate whether differences in gene expression exist in aortas from BAV and TAV patients with AscAA. Keywords: disease state analysis
2007-06-28 | GSE5180 | GEO
Project description:Arterial endothelial cells (ECs) have the ability to respond to mechanical forces exerted by laminar fluid shear stress. This response is of importance, as it is protective against vascular diseases such as atherosclerosis and aortic aneurysms. Mechanical forces are transmitted at the sites of adhesion to the basal membrane as well as cell-cell junctions where protein complexes connect to the cellular cytoskeleton to relay force into the cell. Here we present a novel protein complex that connects junctional VE-cadherin and radial actin filaments to the LINC complex in the nuclear membrane. We show that the scaffold protein AmotL2 is essential for the formation of radial actin filaments and the flow-induced alignment of aortic endothelial cells. The deletion of endothelial AmotL2 alters nuclear shape as well as subcellular positioning. Molecular analysis shows that VE-cadherin is mechanically associated with the nuclear membrane via binding to AmotL2 and Actin. Furthermore, the deletion of AmotL2 in ECs provoked a pro-inflammatory response and abdominal aortic aneurysms (AAA) in the aorta of mice on a normal diet. Remarkably, transcriptome analysis of AAA samples from human patients revealed a negative correlation between AmotL2 expression and inflammation of the aortic intima. These findings provide a conceptual framework regarding how mechanotransduction in the junctions is coupled with vascular diseases.
2023-08-21 | PXD042661 | Pride
Project description:We conducted single-cell RNA sequencing (scRNA-seq) on CD4+ T cells of the aneurysmal aorta and the corresponding splenic cells, in order to unveil the diversity of CD4+ T Cell in Abdominal Aortic Aneurysms.
2024-05-06 | GSE253247 | GEO
Project description:Thoracic aortic aneurysms have a higher prevalence in male patients compared to female patients. Marfan syndrome causes a hereditary form of TAA with dilation of the aortic root. Male patients with Marfan syndrome are more likely than women to have aortic dilation and dissection and mouse models of Marfan syndrome demonstrate larger aortic roots in males compared to females even after adjustment for body size. Similar sex disparities are present in patients and models of abdominal aortic aneurysms where estrogen has been demonstrated to attenuate aneurysm formation perhaps through anti-inflammatory mechanisms. In this study we demonstrate the effects of estrogen on aortic dilation and rupture in a Marfan mouse model and we investigate if these effects operate through suppression of complement components of the immune system.
2024-02-14 | PXD037853 | Pride
Project description:Ascending aortic aneurysms (AscAA) are a life-threatening disease whose molecular basis is poorly understood. Mutations in NOTCH1 have been linked to bicuspid aortic valve (BAV), which is associated with AscAA. Here, we describe a novel role for Notch1 in AscAA. We found that Notch1 haploinsufficiency exacerbated the aneurysmal aortic root dilation seen in the Marfan syndrome mouse model and that heterozygous deletion of Notch1 in the second heart field (SHF) lineage recapitulated this exacerbated phenotype. Lineage tracing analysis showed that loss of Notch1 in the SHF reduces the number of SHF-derived smooth muscle cells in the aortic root, and RNA-seq analysis demonstrated distinct in vivo expression patterns between lineage-specific regions of the ascending aorta. Finally, Notch1+/- mice in a predominantly 129S6 background develop aortic root dilation, indicating that loss of Notch1 independently predisposes to AscAA. These findings are the first to demonstrate a SHF lineage-specific role for Notch1 in AscAA and suggest that genes linked to the development of BAV may also contribute to the associated aortopathy.
2017-09-29 | GSE104365 | GEO
Project description:In the present study, we evaluated miRNA expression profiles of 32 patient aortic aneurysm tissue and plasma samples using Illumina next-generation sequencing platform. A total of 20 miRNA were differentially expressed in tissues, 17 miRNAs - in plasma samples. Differentially expressed miRNAs determined in the present study could be applied for thoracic ascending aneurysm diagnosis.
2020-04-14 | GSE122266 | GEO
Project description:Aortic aneurysm is a highly age- and sex-dependent cardiovascular disease in human, which men are at 4 to 6 times higher risk than women. We recently established an age-dependent animal model in which aldosterone and high salt administration induces aortic aneurysms in 10-month-old wildtype male mice. But whether it exhibits sex differences as in human remains unknown. The current study reports that androgen is a main driver for the sexual dimorphic response to aldosterone and high salt induced aortic aneurysms in mice. To explore the mechanism, aortas were isolated from three groups of mice as described below for transcriptomic profiling.
2024-02-13 | GSE255682 | GEO
Project description:Smooth muscle cell reprogramming in aortic aneurysms
| PRJNA591801 | ENA