Association of TGF-β Canonical Signaling-Related Core Genes With Aortic Aneurysms and Aortic Dissections

Chen, Jicheng; Chang, Rong

doi:10.3389/fphar.2022.888563

Cited by 17 publications

(12 citation statements)

References 118 publications

(130 reference statements)

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“…The TGF-β signaling pathway is significant for the maintenance of normal structure and function of the aorta [35] , and genetic evidence suggests that TGF-β signaling-related genes play an important role in AD, such as mutations in genetic specimens from patients with AD, often accompanied by paradoxically enhanced TGF-β signaling [36] . Chen et al [37] then performed a target sequencing that showed that activation of the TGF-β signaling pathway may be related to the pathogenesis of AD.…”

Section: Resultsmentioning

confidence: 99%

Screening and Analysis of Aortic Dissection Based on Bioinformatics Methods Related Key Genes and Early Prevention and Treatment

Xin,

Liu,

et al. 2024

IJPS

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To Explore Potential Biomarkers in the Development of Aortic DissectionAortic dissection is a serious cardiovascular emergency with a very high early mortality rate, so it is particularly important to develop new targeted therapies to reduce prevalence and improve survival, and we hope to explore potential biomarkers involved in the development of aortic dissection and available pharmaceutical components sensitive to therapeutic targets through bioinformatics technology. First, download the gene expression omnibus dataset (GSE190635), use the affy software package of the R software for data standardization, the limma software package to screen the differential genes, and use the relevant software package to draw the volcano map and heat map of the differential gene; then database for annotation, visualization, and integrated discovery software was used for gene ontology and Kyoto encyclopedia of genes and genomes pathway enrichment analysis. Next, the protein-protein interaction network was further constructed, and the STRING exported data was visualized using Cytoscape software, and finally the hub gene was extracted using cytoHubba and MCODE plugins. Finally, the Coremine medical information retrieval platform was used to screen for possible therapeutic drugs. Through differentially expressed genes analysis, 45 up-regulated differentially expressed genes and 132 down-regulated differentially expressed genes were successfully distinguished from the GSE79768. They are mainly enriched in positive regulation of urine volume, cell activation, extracellular region, lipopeptide binding and nucleotide oligomerization domain-like receptor signaling pathway, etc. Through protein-protein interaction, the top 7 hub genes were ranked, including early growth response protein 1, C-X-C motif chemokine ligand 8, fructo-oligosaccharides, filamin C, toll-like receptor 2, identified integrin alpha 7, myosin light chain-2. Coremine medical was used to retrieve a variety of related drugs, among which recombinant interleukin-6, recombinant tumor necrosis factor family protein, lipopolysaccharide and tyrosine co-regulated the above genes. In this study, 7 differentially expressed genes were identified as potential biomarkers for aortic dissection patients, which may provide new targets for aortic dissection therapy. But this is just the beginning, and we need to carry out experiments to verify the accuracy and feasibility of these results in the future.

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Section: Resultsmentioning

confidence: 99%

Screening and Analysis of Aortic Dissection Based on Bioinformatics Methods Related Key Genes and Early Prevention and Treatment

Xin,

Liu,

et al. 2024

IJPS

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“…In the research literature, studies focused on the role of TGFalpha in AAA are limited, whereas TGF-beta 1 signaling has been intensively studied on this topic. Some hypotheses about the role of TGF-beta 1 in the development of aneurysm have been proposed; however, there are some controversies [45].…”

Section: Discussionmentioning

confidence: 99%

Dysregulations of Key Regulators of Angiogenesis and Inflammation in Abdominal Aortic Aneurysm

Zalewski

Chmiel

Kołodziej

et al. 2023

IJMS

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Abdominal aortic aneurysm (AAA) is a chronic vascular disease caused by localized weakening and broadening of the abdominal aorta. AAA is a clearly underdiagnosed disease and is burdened with a high mortality rate (65–85%) from AAA rupture. Studies indicate that abnormal regulation of angiogenesis and inflammation contributes to progression and onset of this disease; however, dysregulations in the molecular pathways associated with this disease are not yet fully explained. Therefore, in our study, we aimed to identify dysregulations in the key regulators of angiogenesis and inflammation in patients with AAA in peripheral blood mononuclear cells (using qPCR) and plasma samples (using ELISA). Expression levels of ANGPT1, CXCL8, PDGFA, TGFB1, VEGFB, and VEGFC and plasma levels of TGF-alpha, TGF-beta 1, VEGF-A, and VEGF-C were found to be significantly altered in the AAA group compared to the control subjects without AAA. Associations between analyzed factors and risk factors or biochemical parameters were also explored. Any of the analyzed factors was associated with the size of the aneurysm. The presented study identified dysregulations in key angiogenesis- and inflammation-related factors potentially involved in AAA formation, giving new insight into the molecular pathways involved in the development of this disease and providing candidates for biomarkers that could serve as diagnostic or therapeutic targets.

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“…A single transmembrane protein with a cytoplasmic serine/threonine kinase domain. Loss of function mutations in the gene encoding TGF-βR2 cause LDS (25).…”

Section: Tgf-βr2mentioning

confidence: 99%

Markers of extracellular matrix remodeling and systemic inflammation in patients with heritable thoracic aortic diseases

Seim

Holt

Ratajska

et al. 2022

Front. Cardiovasc. Med.

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BackgroundIn approximately 20% of patients with thoracic aortic aneurysms or dissections a heritable thoracic aortic disease (HTAD) is suspected. Several monogenic connective tissue diseases imply high risk of aortic disease, including both non-syndromic and syndromic forms. There are some studies assessing inflammation and extracellular matrix remodeling in patients with non-hereditary aortic disease, but such studies in patients with hereditary diseases are scarce.AimsTo quantify markers of extracellular matrix (ECM) and inflammation in patients with vascular connective tissue diseases versus healthy controls.MethodsPatients with Loeys-Dietz syndrome (LDS, n = 12), Marfan syndrome (MFS, n = 11), and familial thoracic aortic aneurysm 6 (FTAA6, n = 9), i.e., actin alpha 2 (ACTA2) pathogenic variants, were recruited. Exome or genome sequencing was performed for genetic diagnosis. Several markers of inflammation and ECM remodeling were measured in plasma by enzyme immunoassays. Flow cytometry of T-cell subpopulations was performed on a subgroup of patients. For comparison, blood samples were drawn from 14 healthy controls.Results(i) All groups of HTAD patients had increased levels matrix metalloproteinase-9 (MMP-9) as compared with healthy controls, also in adjusted analyses, reflecting altered ECM remodeling. (ii) LDS patients had increased levels of pentraxin 3 (PTX3), reflecting systemic inflammation. (iii) LDS patients have increased levels of soluble CD25, a marker of T-cell activation.ConclusionOur data suggest that upregulated MMP-9, a matrix degrading enzyme, is a common feature of several subgroups of HTAD. In addition, LDS patients have increased levels of PTX3 reflecting systemic and in particular vascular inflammation.

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Association of TGF-β Canonical Signaling-Related Core Genes With Aortic Aneurysms and Aortic Dissections

Cited by 17 publications

References 118 publications

Screening and Analysis of Aortic Dissection Based on Bioinformatics Methods Related Key Genes and Early Prevention and Treatment

Screening and Analysis of Aortic Dissection Based on Bioinformatics Methods Related Key Genes and Early Prevention and Treatment

Dysregulations of Key Regulators of Angiogenesis and Inflammation in Abdominal Aortic Aneurysm

Markers of extracellular matrix remodeling and systemic inflammation in patients with heritable thoracic aortic diseases

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