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 ◽  
...  

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.

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12682
Author(s):  
Ke Si ◽  
Da Lu ◽  
Jianbo Tian

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.


VASA ◽  
2005 ◽  
Vol 34 (4) ◽  
pp. 217-223 ◽  
Author(s):  
Diehm ◽  
Schmidli ◽  
Dai-Do ◽  
Baumgartner

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.


2015 ◽  
Vol 2015 ◽  
pp. 1-6
Author(s):  
Yohei Kawatani ◽  
Yoshitsugu Nakamura ◽  
Yujiro Hayashi ◽  
Tetsuyoshi Taneichi ◽  
Yujiro Ito ◽  
...  

Infectious abdominal aortic aneurysms often present with abdominal and lower back pain, but prolonged fever may be the only symptom. Infectious abdominal aortic aneurysms initially presenting with meningitis are extremely rare; there are no reports of their successful treatment. Cases withStreptococcus pneumoniaeas the causative bacteria are even rarer with a higher mortality rate than those caused by other bacteria. We present the case of a 65-year-old man with lower limb weakness and back pain. Examination revealed fever and neck stiffness. Cerebrospinal fluid showed leukocytosis and low glucose levels. The patient was diagnosed with meningitis and bacteremia caused byStreptococcus pneumoniaeand treated with antibiotics. Fever, inflammatory response, and neurologic findings showed improvement. However, abdominal computed tomography revealed an aneurysm not present on admission. Antibiotics were continued, and a rifampicin soaked artificial vascular graft was implanted. Tissue cultures showed no bacteria, and histological findings indicated inflammation with high leukocyte levels. There were no postoperative complications or neurologic abnormalities. Physical examination, blood tests, and computed tomography confirmed there was no relapse over the following 13 months. This is the first reported case of survival of a patient with an infectious abdominal aortic aneurysm initially presenting with meningitis caused byStreptococcus pneumoniae.


2020 ◽  
Author(s):  
Chuang Li ◽  
Yubo Zhao ◽  
Shuwei Wan ◽  
Yaming Guo ◽  
Mingli Han ◽  
...  

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.


2019 ◽  
Vol 13 (9) ◽  
pp. 430-434
Author(s):  
Ian Peate

This is the second article in a series of articles regarding screening programmes. In this article, an overview of the abdominal aorta is provided. The article also considers the abdominal aortic aneurysm screening programme. Aortic abdominal aneurysm is described. The majority of abdominal aortic aneurysms are asymptomatic; however, if there are any symptoms, these are explained. All four UK countries offer men aged 65 years and over a screening opportunity using an ultrasound scan, the fundamental aspects of abdominal aortic aneurysm screening programmes is offered. It is emphasised that screening is not mandatory in the UK; the man has a right to decline the invitation to attend any screening programme.


Vascular ◽  
2014 ◽  
Vol 23 (4) ◽  
pp. 411-418 ◽  
Author(s):  
Erasmo S da Silva ◽  
Vitor C Gornati ◽  
Ivan B Casella ◽  
Ricardo Aun ◽  
Andre EV Estenssoro ◽  
...  

Objective To analyze the characteristics of patients with abdominal aortic aneurysms referred to a tertiary center and to compare with individuals with abdominal aortic aneurysm found at necropsy. Methods We have retrospectively analyzed the medical records of 556 patients with abdominal aortic aneurysm and 102 cases abdominal aortic aneurysm found at necropsy. Results At univariated analysis, hypertension, tobacco use and maximum diameter were significant risk factors for symptomatic aneurysm, while diabetes tended to be a protective factor for rupture. By logistic regression analysis, the largest transverse diameter was the only one significantly associated with abdominal aortic aneurysm rupture ( p < .0001, odds ratio 1.7, 95% confidence interval 1.481–1.951). Intact abdominal aortic aneurysm found at necropsy showed similarities with outpatients in relation to abdominal aortic aneurysm diameter and risk factors. Conclusion Intact abdominal aortic aneurysm at necropsy and at outpatients setting showed similarities that confirmed that abdominal aortic aneurysm repair is less offered to women, and they died more frequently with intact abdominal aortic aneurysm from other causes.


2021 ◽  
pp. 153857442110226
Author(s):  
Dorota Studzińska ◽  
Mateusz Kózka ◽  
Kamil Polok ◽  
Katarzyna Gronostaj ◽  
Maciej Chwała ◽  
...  

Objective: The aim of our study was to assess the prevalence of renal masses suspected of malignancy and adrenal incidentalomas in patients with abdominal aortic aneurysm based on the computed tomography angiography (CTA). Methods: In the retrospective cross-sectional study, the CTA scans of patients with abdominal aortic aneurysms and thoraco-abdominal aortic aneurysms type II-IV were assessed. Patients with thoraco-abdominal aortic aneurysms type I and V and history of abdominal aortic surgery were excluded from the study. Results: Study group comprised 937 patients with a median age of 73.0 years, 83.8% of whom were male. CTA revealed renal tumors in 11 patients (1.2% of the study population) with a median size of 26 mm (interquartile range 20-50). Adrenal incidentalomas were found in 61 patients (6.5% of the study population). In 20 patients (2.1%) adrenal lesions were found bilaterally. Conclusion: In the described cohort, the renal and adrenal tumors were relatively common findings among patients with abdominal aortic aneurysm and thoraco-abdominal aortic aneurysms type II-IV. Both anaesthesiologists and surgeons should be vigilant about the possibility of such coexistence in order to provide the patients with the best possible perioperative care and an optimal surgical modality.


Vascular ◽  
2017 ◽  
Vol 25 (6) ◽  
pp. 657-665 ◽  
Author(s):  
Vinay Kansal ◽  
Sudhir Nagpal ◽  
Prasad Jetty

Objective Endovascular aneurysm repair for ruptured abdominal aortic aneurysm is being increasingly applied as the intervention of choice. The purpose of this study was to determine whether survival and reintervention rates after ruptured abdominal aortic aneurysm vary between endograft devices. Methods This cohort study identified all ruptured abdominal aortic aneurysms performed at The Ottawa Hospital from January 1999 to May 2015. Data collected included patient demographics, stability index at presentation, adherence to device instructions for use, endoleaks, reinterventions, and mortality. Kruskal–Wallis test was used to compare outcomes between groups. Mortality outcomes were assessed using Kaplan–Meier survival analysis, and multivariate Cox regression modeling. Results One thousand sixty endovascular aneurysm repairs were performed using nine unique devices. Ninety-six ruptured abdominal aortic aneurysms were performed using three devices: Cook Zenith ( n = 46), Medtronic Endurant ( n = 33), and Medtronic Talent ( n = 17). The percent of patients presented in unstable or extremis condition was 30.2, which did not differ between devices. Overall 30-day mortality was 18.8%, and was not statistically different between devices ( p = 0.16), although Medtronic Talent had markedly higher mortality (35.3%) than Cook Zenith (15.2%) and Medtronic Endurant (15.2%). AUI configuration was associated with increased 30-day mortality (33.3% vs. 12.1%, p = 0.02). Long-term mortality and graft-related reintervention rates at 30 days and 5 years were similar between devices. Instructions for use adherence was similar across devices, but differed between the ruptured abdominal aortic aneurysm and elective endovascular aneurysm repair cohorts (47.7% vs. 79.0%, p < 0.01). Notably, two patients who received Medtronic Talent grafts underwent open conversion >30 days post-endovascular aneurysm repair ( p = 0.01). Type 1 endoleak rates differed significantly across devices (Cook Zenith 0.0%, Medtronic Endurant 18.2%, Medtronic Talent 17.6%, p = 0.01). Conclusion Although we identified device-related differences in endoleak rates, there were no significant differences in reintervention rates or mortality outcomes. Favorable outcomes of Cook Zenith and Medtronic Endurant over Medtronic Talent reflect advances in endograft technology and improvements in operator experience over time. Results support selection of endograft by operator preference for ruptured abdominal aortic aneurysm.


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