scholarly journals Predicting Abdominal Aortic Aneurysm Target Genes by Level-2 Protein-Protein Interaction

PLoS ONE ◽  
2015 ◽  
Vol 10 (10) ◽  
pp. e0140888 ◽  
Author(s):  
Kexin Zhang ◽  
Tuoyi Li ◽  
Yi Fu ◽  
Qinghua Cui ◽  
Wei Kong
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Protein Interaction ◽  
Target Genes ◽  
Protein Protein Interaction ◽  
Abdominal Aortic ◽  
Level 2

scholarly journals Integrated analysis and the identification of a circRNA-miRNA-mRNA network in the progression of abdominal aortic aneurysm

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12682
Author(s):  
Ke Si ◽  
Da Lu ◽  
Jianbo Tian
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Protein Interaction ◽  
Protein Interaction Network ◽  
Interaction Network ◽  
Hub Genes ◽  
Tissue Samples ◽  
Protein Protein Interaction ◽  
Abdominal Aortic ◽  
Protein Protein Interaction Network

Background Abdominal aortic aneurysm (AAA) is a disease commonly seen in the elderly. The aneurysm diameter increases yearly, and the larger the AAA the higher the risk of rupture, increasing the risk of death. However, there are no current effective interventions in the early stages of AAA. Methods Four gene expression profiling datasets, including 23 normal artery (NOR) tissue samples and 97 AAA tissue samples, were integrated in order to explore potential molecular biological targets for early intervention. After preprocessing, differentially expressed genes (DEGs) between AAA and NOR were identified using LIMMA package. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis were conducted using the DAVID database. The protein-protein interaction network was constructed and hub genes were identified using the STRING database and plugins in Cytoscape. A circular RNA (circRNA) profile of four NOR tissues versus four AAA tissues was then reanalyzed. A circRNA-miRNA-mRNA interaction network was constructed after predictions were made using the Targetscan and Circinteractome databases. Results A total of 440 DEGs (263 up-regulated and 177 down-regulated) were identified in the AAA group, compared with the NOR group. The majority were associated with the extracellular matrix, tumor necrosis factor-α, and transforming growth factor-β. Ten hub gene-encoded proteins (namely IL6, RPS27A, JUN, UBC, UBA52, FOS, IL1B, MMP9, SPP1 and CCL2) coupled with a higher degree of connectivity hub were identified after protein‐protein interaction network analysis. Our results, in combination with the results of previous studies revealed that miR-635, miR-527, miR-520h, miR-938 and miR-518a-5p may be affected by circ_0005073 and impact the expression of hub genes such as CCL2, SPP1 and UBA52. The miR-1206 may also be affected by circ_0090069 and impact RPS27A expression. Conclusions This circRNA-miRNA-mRNA network may perform critical roles in AAA and may be a novel target for early intervention.

scholarly journals Construction of the circRNA-miRNA-mRNA Regulatory Network of an Abdominal Aortic Aneurysm to Explore Its Potential Pathogenesis

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Hao Zhang ◽  
Ce Bian ◽  
Simei Tu ◽  
Fanxing Yin ◽  
Panpan Guo ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Protein Interaction ◽  
Abdominal Aortic Aneurysms ◽  
Aortic Aneurysms ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Hub Genes ◽  
Protein Protein Interaction ◽  
Abdominal Aortic

Background. Abdominal aortic aneurysm (AAA) is a progressive cardiovascular disease, which is a permanent and localized dilatation of the abdominal aorta with potentially fatal consequence of aortic rupture. Dysregulation of circRNAs is correlated with the development of various pathological events in cardiovascular diseases. However, the function of circRNAs in abdominal aortic aneurysm (AAA) is unknown and remains to be explored. This study is aimed at determining the regulatory mechanisms of circRNAs in AAAs. This study was aimed at exploring the underlying molecular mechanisms of abdominal aortic aneurysms based on the competing endogenous RNA (ceRNA) regulatory hypothesis of circRNA, miRNA, and mRNA. Methods. The expression profiles of circRNAs (GSE144431), miRNAs (GSE62179), and mRNAs (GSE7084, GSE57691, and GSE47472) in human tissue sample from the aneurysm group and normal group were obtained from the Gene Expression Omnibus database, respectively. The circRNA-miRNA-mRNA network was constructed by using Cytoscape 3.7.2 software; then, the protein-protein interaction (PPI) network was constructed by using the STRING database, and the hub genes were identified by using the cytoHubba plug-in. The circRNA-miRNA-hub gene regulatory subnetwork was formed to understand the regulatory axis of hub genes in AAAs. Results. The present study identified 40 differentially expressed circRNAs (DECs) in the GSE144431, 90 differentially expressed miRNAs (DEmiRs) in the GSE62179, and 168 differentially expressed mRNAs (DEGs) with the same direction regulation (130 downregulated and 38 upregulated) in the GSE7084, GSE57691, and GSE47472 datasets identified regarding AAAs. The miRNA response elements (MREs) of three DECs were then predicted. Four overlapping miRNAs were obtained by intersecting the predicted miRNA and DEmiRs. Then, 17 overlapping mRNAs were obtained by intersecting the predicted target mRNAs of 4 miRNAs with 168 DEGs. Furthermore, the circRNA-miRNA-mRNA network was constructed through 3 circRNAs, 4 miRNAs, and 17 mRNAs, and three hub genes (SOD2, CCR7, and PGRMC1) were identified. Simultaneously, functional enrichment and pathway analysis were performed within genes in the circRNA-miRNA-mRNA network. Three of them (SOD2, CCR7, and PGRMC1) were suggested to be crucial based on functional enrichment, protein-protein interaction, and ceRNA network analysis. Furthermore, the expression of SOD2 and CCR7 may be regulated by hsa_circ_0011449/hsa_circ_0081968/hsa-let-7f-5p; the expression of PGRMC1 may be regulated by hsa_circ_0011449/hsa_circ_0081968-hsa-let-7f-5p/hsa-let-7e-5p. Conclusion. In conclusion, the ceRNA interaction axis we identified may be an important target for the treatment of abdominal aortic aneurysms. This study provided further understanding of the potential pathogenesis from the perspective of the circRNA-related competitive endogenous RNA network in AAAs.

Expression characteristics of exosomal long non-coding RNA in abdominal aortic aneurysm

2020 ◽  
Author(s):  
Chuang Li ◽  
Yubo Zhao ◽  
Shuwei Wan ◽  
Yaming Guo ◽  
Mingli Han ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Calcium Signaling ◽  
Target Genes ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Abdominal Aortic ◽  
Wide Range ◽  
Significant Difference ◽  
Internal Mechanism

Abstract Background and objective:Abdominal aortic aneurysm(AAA) is one of the important causes of morbidity and mortality in middle-aged and elderly people. Although the understanding of the physiology and pathology of AAA has been improved, the potential molecular mechanism of AAA is still unclear. The existing evidence confirms that exosomal lncRNAs have a wide range of biological functions, and its regulatory disorders are related to the occurrence of diseases such as AAA, but the internal mechanism is not clear. The main purpose of this study is to screen the differentially expressed lncRNAs in exosomes between normal people and patients with AAA and to understand its internal mechanism.Materials and methods:The plasma of a healthy control group and patients with abdominal aortic aneurysm was collected, and the lncRNAs of exosomes were extracted and sequenced. Differential expression was assessed by DEseq using read counts as input and chosen according to the criteria of |log2(fold change)| > 1 and adjusted p-value < 0.05. Based on the Kyoto encyclopedia of genes and genomes (KEGG) and biological pathway and gene ontology (GO) functional enrichment analysis, the target genes were analyzed, and the correlation between lncRNA and target genes was analyzed.Result:We screened 45 species differentially expressed lncRNAs and found pathway significantly related to these genes, namely metabolic pathways, calcium signaling pathways and protein processing in endoplasmic reticulum and They play a significant and important role in the metabolic process and the cell signaling.Conclusion:There was significant difference in expression of exosomal lncRNAs between normal subjects and AAA patients. LncRNAs in exosomes regulate in the progress of AAA by activating metabolic pathway and calcium signaling pathway, but the specific mechanism is not clear and needs to be further explored.

scholarly journals Quantitative Aortic Distensibility Measurement Using CT in Patients with Abdominal Aortic Aneurysm: Reproducibility and Clinical Relevance

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Yunfei Zha ◽  
Gongling Peng ◽  
Liang Li ◽  
Chunying Yang ◽  
Xuesong Lu ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Clinical Relevance ◽  
Intraclass Correlation ◽  
Endovascular Aneurysm Repair ◽  
Aortic Distensibility ◽  
Infrarenal Abdominal Aortic Aneurysm ◽  
Abdominal Aortic ◽  
Level 1 ◽  
Level 2

Purpose.To investigate the reproducibility of aortic distensibility (D) measurement using CT and assess its clinical relevance in patients with infrarenal abdominal aortic aneurysm (AAA).Methods.54 patients with infrarenal abdominal aortic aneurysm were studied to determine their distensibility by using 64-MDCT. Aortic cross-sectional area changes were determined at two positions of the aorta, immediately below the lowest renal artery (level 1.) and at the level of its maximal diameter (level 2.) by semiautomatic segmentation. Measurement reproducibility was assessed using intraclass correlation coefficient (ICC) and Bland-Altman analyses. Stepwise multiple regression analysis was performed to assess linear associations between aorticDand anthropometric and biochemical parameters.Results.A mean distensibility ofDlevel  1.=(1.05±0.22)×10-5  Pa-1andDlevel  2.=(0.49±0.18)×10-5  Pa-1was found. ICC proved excellent consistency between readers over two locations: 0.92 for intraobserver and 0.89 for interobserver difference in level 1. and 0.85 and 0.79 in level 2. Multivariate analysis of all these variables showed sac distensibility to be independently related (R2=0.68) to BMI, diastolic blood pressure, and AAA diameter.Conclusions.Aortic distensibility measurement in patients with AAA demonstrated high inter- and intraobserver agreement and may be valuable when choosing the optimal dimensions graft for AAA before endovascular aneurysm repair.

scholarly journals MicroRNASeq Target Analysis and Validation by Real-Time PCR in Abdominal Aortic Aneurysm

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Willa Sasso ◽  
Leni Moldovan ◽  
Michael Murphy
Keyword(s):  
Risk Factor ◽  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Cigarette Smoke ◽  
Target Genes ◽  
Inflammatory Factors ◽  
Cigarette Smoke Exposure ◽  
Aortic Tissue ◽  
Epigenetic Changes ◽  
Abdominal Aortic

Background/ Objective: Abdominal aortic aneurysm (AAA) is an epigenetic event characterized by chronic inflammation and degeneration of the aortic wall leading to catastrophic rupture. Cigarette smoke exposure is the greatest environmental risk factor associated with AAA development. MicroRNAs (miRNA) regulate gene expression and may play a role in smoking-induced aortic inflammation. Epigenetic changes could include dysregulation of miRNA, causing post-transcriptional abnormalities pathogenic to AAA.     Methods: miRNA was extracted from plasma of 24 AAA patients and 7 risk factor matched (RFM) patients and analyzed by RNA sequencing. We compared previous (PS) and current smokers (CS) within and between both patient cohorts. Differential expression of miRNAs was analyzed by ANOVA (p≤ 0.05). Potential targets of significant differentially expressed miRNAs were predicted using cross-analysis of TargetScan and miRanda databases.     Results: Analysis revealed 7 significantly different miRNAs between AAA CS and AAA PS and 6 significantly different miRNAs between RFM CS and RFM PS. Of greatest significance, hsa-miR-223-3p was significantly downregulated as an effect of smoking cessation in AAA PS compared to AAA CS (p=0.000263), while also showing clinically relevant expression levels. Target genes of hsa-miR-223-3p include pro-inflammatory factors IL-6, TNFα, TGFβ, and MCP-1. Speculatively, as tissue levels of miR-223 tend to inversely correlate with plasma levels, we could hypothesize that the observed plasma upregulation of hsa-miR-223-3p in AAA CS contributes to the pro-inflammatory microenvironment of aortic tissue.     Conclusion: Cigarette smoke contributes to epigenetic changes impacting factors of immune regulation or inflammation, eventually leading to disease states such as AAA. Inflammatory-related hsa-miR-223-3p is upregulated in AAA CS, suggesting its potential role in the disease course.     Implications: Upregulation of hsa-miR-223-3p in AAA CS offers a link between disease state and the number one environmental factor attributed to AAA. This signature miRNA could serve as a biomarker for AAA or as a potential therapy target.  

scholarly journals Dysregulation of microRNAs and target genes networks in human abdominal aortic aneurysm tissues

PLoS ONE ◽  
2019 ◽  
Vol 14 (9) ◽  
pp. e0222782 ◽  
Author(s):  
Neire Niara Ferreira de Araujo ◽  
Hui Tzu Lin-Wang ◽  
Juliana de Freitas Germano ◽  
Pedro Silvio Farsky ◽  
Andre Feldman ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Target Genes ◽  
Abdominal Aortic

scholarly journals Simvastatin Treatment Upregulates HO-1 in Patients with Abdominal Aortic Aneurysm but Independently of Nrf2

2018 ◽  
Vol 2018 ◽  
pp. 1-16 ◽  
Author(s):  
Aleksandra Piechota-Polanczyk ◽  
Aleksandra Kopacz ◽  
Damian Kloska ◽  
Branislav Zagrapan ◽  
Christoph Neumayer ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Protein Level ◽  
Target Genes ◽  
Cell Types ◽  
Vasa Vasorum ◽  
Heme Oxygenase 1 ◽  
Simvastatin Treatment ◽  
Abdominal Aortic

Heme oxygenase-1 (HO-1), encoded by HMOX1 gene and regulated by Nrf2 transcription factor, is a cytoprotective enzyme. Its deficiency may exacerbate abdominal aortic aneurysm (AAA) development, which is also often associated with hyperlipidemia. Beneficial effects of statins, the broadly used antilipidemic drugs, were attributed to modulation of Nrf2/HO-1 axis. However, the effect of statins on Nrf2/HO-1 pathway in patients with AAA has not been studied yet. We analyzed AAA tissue from patients treated with simvastatin (N = 28) or without statins (N = 14). Simvastatin treatment increased HO-1 protein level in AAA, both in endothelial cells (ECs) and in smooth muscle cells (SMCs), but increased Nrf2 localization was restricted only to vasa vasorum. Nrf2 target genes HMOX1, NQO1, and GCLM expression remained unchanged in AAA. In vitro studies showed that simvastatin raises HO-1 protein level slightly in ECs and to much higher extent in SMCs, which is not related to Nrf2/ARE activation, although HMOX1 expression is upregulated by simvastatin in both cell types. In conclusion, simvastatin-induced modulation of HO-1 level in ECs and SMCs in vitro is not related to Nrf2/ARE activity. Likewise, divergent HO-1 and Nrf2 localization together with stable expression of Nrf2 target genes, including HMOX1, in AAA tissue denotes Nrf2 independency.

scholarly journals Identification of key genes and pathways in abdominal aortic aneurysm by integrated bioinformatics analysis

2019 ◽  
Vol 48 (4) ◽  
pp. 030006051989443
Author(s):  
Yihai Liu ◽  
Xixi Wang ◽  
Hongye Wang ◽  
Tingting Hu
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Single Cell ◽  
Target Genes ◽  
Rna Seq ◽  
Ppi Network ◽  
Hub Genes ◽  
Microarray Profile ◽  
Abdominal Aortic ◽  
Key Genes

Objectives To identify key genes associated with abdominal aortic aneurysm (AAA) by integrating a microarray profile and a single-cell RNA-seq dataset. Methods The microarray profile of GSE7084 and the single-cell RNA-seq dataset were obtained from the Gene Express Omnibus database. Differentially expressed genes (DEGs) were chosen using the R package and annotated by Gene Ontology and Kyoto Encyclopedia of Genes and Genomics analysis. The hub genes were identified based on their degrees of interaction in the protein-protein interaction (PPI) network. Expression of hub genes was determined using single-cell RNA-seq analysis. Results In total, 507 upregulated and 842 downregulated DEGs were identified and associated with AAA. The upregulated DEGs were enriched into 9 biological processes and 10 biological pathways, which were closely involved in the pathogenesis and progression of AAA. Based on the PPI network, we focused on six hub genes, four of which were novel target genes compared with the known aneurysm gene database. Using single-cell RNA-seq analysis, we explored the four genes expressed in vascular cells of AAA: CANX, CD44, DAXX, and STAT1. Conclusions We identified key genes that may provide insight into the mechanism of AAA pathogenesis and progression and that have potential to be therapeutic targets.

Current evidence and prospects for medical treatment of abdominal aortic aneurysms

VASA ◽  
2005 ◽  
Vol 34 (4) ◽  
pp. 217-223 ◽  
Author(s):  
Diehm ◽  
Schmidli ◽  
Dai-Do ◽  
Baumgartner
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Medical Treatment ◽  
Endovascular Treatment ◽  
Abdominal Aortic Aneurysms ◽  
Aortic Aneurysms ◽  
Current Evidence ◽  
Significant Morbidity ◽  
Abdominal Aortic ◽  
Risk Of Rupture

Abdominal aortic aneurysm (AAA) is a potentially fatal condition with risk of rupture increasing as maximum AAA diameter increases. It is agreed upon that open surgical or endovascular treatment is indicated if maximum AAA diameter exceeds 5 to 5.5cm. Continuing aneurysmal degeneration of aortoiliac arteries accounts for significant morbidity, especially in patients undergoing endovascular AAA repair. Purpose of this review is to give an overview of the current evidence of medical treatment of AAA and describe prospects of potential pharmacological approaches towards prevention of aneurysmal degeneration of small AAAs and to highlight possible adjunctive medical treatment approaches after open surgical or endovascular AAA therapy.

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