High-throughput sequencing analysis of miRNAs expression profiles in the thoracic ascending aortic aneurysm (TAA) tissues and plasma samples.
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE122266 | GEO | 2020/04/14
REPOSITORIES: GEO
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Project description:High-throughput sequencing analysis of miRNAs expression profiles in the thoracic ascending aortic aneurysm (TAA) tissues and plasma samples.
| PRJNA504426 | ENA
Project description:To determine how gene expression is altered in aorta tissue in response to aortic aneurysm disease. Thoracic or abdominal aorta tissue was isolated from patients requiring surgery due to aortic aneurysm or other (control) reason.
2024-10-09 | GSE202267 | 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: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:In this study, we identified various cell clusters in human normal/sporadic TAA ascending aorta samples by single-cell RNA sequencing (scRNA-seq), and discovered the senescent vascular smooth muscle cells (VSMCs) significantly increased in TAA samples. Then we explored the molecular basis of TAA progression, and recognized the key regulators and pathways involved in the TAA progression regulation.
2023-12-01 | GSE143921 | 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:ImportanceThe risk of adverse events from ascending thoracic aorta aneurysm (TAA) is poorly understood but drives clinical decision-making.ObjectiveTo evaluate the association of TAA size with outcomes in nonsyndromic patients in a large non-referral-based health care delivery system.Design, setting, and participantsThe Kaiser Permanente Thoracic Aortic Aneurysm (KP-TAA) cohort study was a retrospective cohort study at Kaiser Permanente Northern California, a fully integrated health care delivery system insuring and providing care for more than 4.5 million persons. Nonsyndromic patients from a regional TAA safety net tracking system were included. Imaging data including maximum TAA size were merged with electronic health record (EHR) and comprehensive death data to obtain demographic characteristics, comorbidities, medications, laboratory values, vital signs, and subsequent outcomes. Unadjusted rates were calculated and the association of TAA size with outcomes was evaluated in multivariable competing risk models that categorized TAA size as a baseline and time-updated variable and accounted for potential confounders. Data were analyzed from January 2018 to August 2021.ExposuresTAA size.Main outcomes and measuresAortic dissection (AD), all-cause death, and elective aortic surgery.ResultsOf 6372 patients with TAA identified between 2000 and 2016 (mean [SD] age, 68.6 [13.0] years; 2050 female individuals [32.2%] and 4322 male individuals [67.8%]), mean (SD) initial TAA size was 4.4 (0.5) cm (828 individuals [13.0% of cohort] had initial TAA size 5.0 cm or larger and 280 [4.4%] 5.5 cm or larger). Rates of AD were low across a mean (SD) 3.7 (2.5) years of follow-up (44 individuals [0.7% of cohort]; incidence 0.22 events per 100 person-years). Larger initial aortic size was associated with higher risk of AD and all-cause death in multivariable models, with an inflection point in risk at 6.0 cm. Estimated adjusted risks of AD within 5 years were 0.3% (95% CI, 0.3-0.7), 0.6% (95% CI, 0.4-1.3), 1.5% (95% CI, 1.2-3.9), 3.6% (95% CI, 1.8-12.8), and 10.5% (95% CI, 2.7-44.3) in patients with TAA size of 4.0 to 4.4 cm, 4.5 to 4.9 cm, 5.0 to 5.4 cm, 5.5 to 5.9 cm, and 6.0 cm or larger, respectively, in time-updated models. Rates of the composite outcome of AD and all-cause death were higher than for AD alone, but a similar inflection point for increased risk was observed at 6.0 cm.Conclusions and relevanceIn a large sociodemographically diverse cohort of patients with TAA, absolute risk of aortic dissection was low but increased with larger aortic sizes after adjustment for potential confounders and competing risks. Our data support current consensus guidelines recommending prophylactic surgery in nonsyndromic individuals with TAA at a 5.5-cm threshold.
| S-EPMC9535537 | biostudies-literature
Project description:We report dynamic temporal and spatial smooth muscle cell phenotype modulation using aortic single cell RNA sequencing in a murine model of Marfan syndrome (Fbn1C1041G/+) and littermate controls. Aortic root/ascending aortic tissue samples from both genotypes were studied at 4 and 24 weeks of age. The non-aneurysmal descending thoracic aorta was also studied at 24 weeks. Finally human aortic tissue from a Marfan syndrome patient undergoing aneurysm repair surgery was studied.
2020-06-30 | GSE153534 | GEO
Project description:Plasma biomarkers that identify abdominal aortic aneurysm (AAA) rupture risk would greatly assist in stratifying patients with small aneurysms. Identification of such biomarkers has hitherto been unsuccessful over a range of studies using different methods. The present study used an alternative proteomic approach to find new, potential plasma AAA biomarker candidates. Pre-fractionated plasma samples from twelve patients with AAA and eight matched controls without aneurysm were analyzed by mass spectrometry applying a tandem mass tag (TMT) technique. Eight proteins were differentially regulated in patients compared to controls, including decreased levels of the enzyme bleomycin hydrolase. The down-regulation of this enzyme was confirmed in an extended validation study using an ELISA assay. The TMT-based proteomic approach thus identified novel potential plasma biomarkers for AAA.
2018-10-22 | PXD011309 | Pride
Project description:Cellular communication network factor 2 (CCN2/CTGF) has been traditionally described as a downstream mediator of other profibrotic factors including transforming growth factor (TGF)-β and angiotensin II. However, recent evidence from our group demonstrated the direct role of CCN2 in maintaining aortic wall homeostasis and acute and lethal aortic aneurysm development induced by angiotensin II in the absence of CCN2 in mice. In order to translate these findings to humans, we evaluated the potential association between three polymorphisms in the CCN2 gene and the presence of a thoracic aortic aneurysm (TAA). Patients with and without TAA retrospectively selected were genotyped for rs6918698, rs9402373 and rs12526196 polymorphisms related to the CCN2 gene. Multivariable logistic regression models were performed. In our population of 366 patients (69 with TAA), no associations were found between rs6918698 and rs9402373 and TAA. However, the presence of one C allele from rs12526196 was associated with TAA comparing with the TT genotype, independently of risk factors such as sex, age, hypertension, type of valvulopathy and the presence of a bicuspid aortic valve (OR = 3.17; 95% CI = 1.30-7.88; p = 0.011). In conclusion, we demonstrated an association between the C allele of rs12526196 in the CCN2 gene and the presence of TAA. This study extrapolates to humans the relevance of CCN2 in aortic aneurysm observed in mice and postulates, for the first time, a potential protective role to CCN2 in aortic aneurysm pathology. Our results encourage future research to explore new variants in the CCN2 gene that could be predisposed to TAA development.
| S-EPMC9740045 | biostudies-literature