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 Osteopontin N-Terminal Function in an Abdominal Aortic Aneurysm From Apolipoprotein E-Deficient Mice

2021 ◽  
Vol 9 ◽  
Author(s):  
Hongyang Liu ◽  
Ying Zhang ◽  
Wei Song ◽  
Yancui Sun ◽  
Yinong Jiang
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Inflammatory Factors ◽  
Aortic Tissue ◽  
Binding Motif ◽  
Ang Ii ◽  
Histological Changes ◽  
N Protein ◽  
Abdominal Aortic

The cleavage of osteopontin (OPN) by thrombin results in an N-terminal fragment (OPN-N), which exposes a cryptic integrin-binding motif that promotes the adherence of cells, and plays a proinflammatory role. However, the effect of OPN-N on abdominal aortic aneurysm (AAA) remains unknown. The aim of this study was to investigate the expression of OPN-N in aortic tissue samples obtained from patients, who underwent acute aortic dissection (AD), and normal aorta, effect of OPN-N on angiotensin (Ang) II-induced AAA in mice, and relationship between OPN-N and pyroptosis-related inflammatory factors in vitro. Hematoxylin and eosin staining was conducted to detect histological changes. Next, we detected the expression of the OPN-N protein. Additionally, ApoE−/− mice were divided into four groups: control, control + M5Ab (to block the OPN-N function in mice), Ang II, and Ang II + M5Ab. All mice were euthanized after a 28-day infusion and whole aortas, including thoracic and abdominal aortas, were collected for morphological and histological analysis of the AAA. The OPN-N protein expression was higher in patients with AD than in normal individuals, while histological changes in the aortas of Ang II mice were suppressed in Ang II + M5Ab mice. The expression of OPN-N, NOD-, LRR-, and pyrin domain-containing protein 3, pro-Caspase-1, ASC, Gasdermin-d, interleukin (IL)-18, IL-1β, matrix metalloproteinase (MMP) 2, and MMP9 was lower in the Ang II + M5Ab group than in the Ang II group. The gene expression of monocyte chemoattractant protein-1, IL-6, and tumor necrosis factor-α was suppressed in the aortic tissues of the Ang II + M5Ab group compared with the Ang II group. Moreover, the expression of α-smooth muscle actin was lower in the Ang II group than in the Ang II + M5Ab group. In vitro results showed that the increase in the expression of pyroptosis-related inflammatory factors induced by OPN was mediated through the nuclear factor (NF)-κB pathway. In conclusion, OPN-N promotes AAA by increasing the expression of pyroptosis-related inflammatory factors through the NF-κB pathway, inflammation, and extracellular matrix degradation. These results highlight the potential of OPN-N as a new therapeutic target to prevent AAA expansion.

The Obesity-associated Risk in Open and Endovascular Repair of Abdominal Aortic Aneurysm

2019 ◽  
Vol 25 (18) ◽  
pp. 2033-2037 ◽  
Author(s):  
Djordje Radak ◽  
Slobodan Tanaskovic ◽  
Mihailo Neskovic
Keyword(s):  
Risk Factor ◽  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Treatment Option ◽  
Morbidly Obese ◽  
Complication Rates ◽  
Obese Patients ◽  
Invasive Treatment ◽  
Abdominal Aortic ◽  
The Subject

: The rising pandemic of obesity in modern society should direct attention to a more comprehensive approach to abdominal aortic aneurysm (AAA) treatment in the affected population. Although overweight patients are considered prone to increased surgical risk, studies on the subject did not confirm or specify the risks well enough. : Associated comorbidities inevitably lead to a selection bias leaning towards endovascular abdominal aortic repair (EVAR), as a less invasive treatment option, which makes it hard to single out obesity as an independent risk factor. The increased technical difficulty often results in prolonged procedure times and increased blood loss. Several smaller studies and two analyses of national registries, including 7935 patients, highlighted the advantages of EVAR over open repair (OR) of abdominal aortic aneurysm, especially in morbidly obese population (relative risk reduction up to 47%). On the other hand, two other studies with 1374 patients combined, concluded that EVAR might not have an advantage over OR in obese patients (P = 0.52). Obesity is an established risk factor for wound infection after both EVAR and OR, which is associated with longer length of stay, subsequent major operations, and a higher rate of graft failure. Percutaneous EVAR technique could present a promising solution to reducing this complication. : EVAR seems like a more feasible treatment option than OR for obese patients with AAA, due to lower overall morbidity and mortality rates, as well as reduced wound-related complication rates. However, there is a clear lack of high-quality evidence on the subject, thus future prospective trials are needed to confirm this advantage.

scholarly journals Prior Cardiac and Thoracic Aortic Surgery as a Complication Risk Factor for Abdominal Aortic Aneurysm Repair

2012 ◽  
Vol 76 (6) ◽  
pp. 1380-1384 ◽  
Author(s):  
Kota Yamamoto ◽  
Toshihiro Fukui ◽  
Shigefumi Matsuyama ◽  
Minoru Tabata ◽  
Haruo Aramoto ◽  
...  
Keyword(s):  
Risk Factor ◽  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Aortic Surgery ◽  
Abdominal Aortic Aneurysm Repair ◽  
Thoracic Aortic Surgery ◽  
Complication Risk ◽  
Abdominal Aortic ◽  
Aneurysm Repair ◽  
Aortic Aneurysm Repair

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.

Abdominal aortic aneurysm repair and colonic infarction: a risk factor appraisal

2007 ◽  
Vol 9 (2) ◽  
pp. 166-172 ◽  
Author(s):  
P. Neary ◽  
C. Hurson ◽  
D. O. Briain ◽  
A. Brabazon ◽  
D. Mehigan ◽  
...  
Keyword(s):  
Risk Factor ◽  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Abdominal Aortic Aneurysm Repair ◽  
Abdominal Aortic ◽  
Aneurysm Repair ◽  
Aortic Aneurysm Repair
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