scholarly journals Tunica-Specific Transcriptome of Abdominal Aortic Aneurysm and the Effect of Intraluminal Thrombus, Smoking, and Diameter Growth Rate

2020 ◽  
Vol 40 (11) ◽  
pp. 2700-2713
Author(s):  
Moritz Lindquist Liljeqvist ◽  
Rebecka Hultgren ◽  
Otto Bergman ◽  
Christina Villard ◽  
Malin Kronqvist ◽  
...  

Objective: There is no medical treatment to prevent abdominal aortic aneurysm (AAA) growth and rupture, both of which are linked to smoking. Our objective was to map the tunica-specific pathophysiology of AAA with consideration of the intraluminal thrombus, age, and sex, and to subsequently identify which mechanisms were linked to smoking and diameter growth rate. Approach and Results: Microarray analyses were performed on 246 samples from 76 AAA patients and 13 controls. In media and adventitia, there were 5889 and 2701 differentially expressed genes, respectively. Gene sets related to adaptive and innate immunity were upregulated in both tunicas. Media-specific gene sets included increased matrix disassembly and angiogenesis, as well as decreased muscle cell development, contraction, and differentiation. Genes implicated in previous genome-wide association studies were dysregulated in media. The intraluminal thrombus had a pro-proteolytic and proinflammatory effect on the underlying media. Active smoking resulted in increased inflammation, oxidative stress, and angiogenesis in all tissues and enriched lipid metabolism in adventitia. Processes enriched with active smoking in control aortas overlapped to a high extent with those differentially expressed between AAAs and controls. The AAA diameter growth rate (n=24) correlated with T- and B-cell expression in media, as well as lipid-related processes in the adventitia. Conclusions: This tunica-specific analysis of gene expression in a large study enabled the detection of features not previously described in AAA disease. Smoking was associated with increased expression of aneurysm-related processes, of which adaptive immunity and lipid metabolism correlated with growth rate.

2015 ◽  
Vol 22 (3) ◽  
pp. 406-412 ◽  
Author(s):  
Eleni Metaxa ◽  
Nikolaos Kontopodis ◽  
Konstantinos Tzirakis ◽  
Christos V. Ioannou ◽  
Yannis Papaharilaou

2021 ◽  
Vol 70 ◽  
pp. 425-433 ◽  
Author(s):  
Jon Unosson ◽  
Dick Wågsäter ◽  
Niclas Bjarnegård ◽  
Rachel De Basso ◽  
Martin Welander ◽  
...  

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 244 (18) ◽  
pp. 1648-1657
Author(s):  
Yuan Li ◽  
Dan Yang ◽  
Bo Sun ◽  
Xu Zhang ◽  
Fangda Li ◽  
...  

As a common disease, abdominal aortic aneurysm (AAA) features permanently progressively dilated abdominal aorta. Various cytokines are implicated in AAA pathogenesis. Clarification of involved cytokines combined with functional analysis may provide new insights into AAA pathogenesis. Using a mouse model, this study analyzed the cytokine profiles in AAA. Cytokines were measured in AAA tissues of saline control or angiotensin II-treated ApoE−/− mice using an antibody array of 200 cytokines, cytokine receptors, and related proteins. Statistical analysis revealed that 21 of 200 proteins were differentially expressed in AAA. These differentially expressed proteins were subjected to function and pathway enrichment analysis, which revealed that leukocyte migration and positive regulation of cell adhesion were the most significant biological processes. Specific signaling pathways, including Janus kinase/signal transducers and activators of transcription and cytokine–cytokine receptor interaction, were prominent in Kyoto encyclopedia of genes and genomes pathway enrichment analysis. Importantly, our data identified cytokines which had not previously been illustrated in AAA pathogenic pathways. Bivariate correlation analysis between these cytokines and protease activity showed that granulocyte colony-stimulating factor (G-CSF), macrophage inflammatory protein 1 g, cardiotrophin 1, milk fat globule-EGF factor 8 protein, interleukin 33, and periostin were positively correlated with matrix metalloprotease 1 (MMP-1), MMP-9, cathepsin B, and cathepsin L. G-CSF was positively correlated with cathepsin L. In conclusion, these results demonstrate that cytokine profile is significantly altered in AAA, and that the newly identified crucial cytokines may function potentially in AAA pathogenesis. Impact statement Various cytokines are known contributors to abdominal aortic aneurysm (AAA) pathologic processes, but the mechanisms underlying the pathogenesis remains unclear. We illustrated the altered cytokine profiles in AAA by high throughput antibody array of 200 cytokines, cytokine receptors and related proteins, as well as bioinformatics analysis of differentially expressed proteins in lesion tissues from AAA mice infused with angiotensin II. Functional analyses of differentially expressed cytokines showed clustering on cell migration and adhesion processes. More importantly, crucial cytokines whose association with AAA formation had not been established were identified. Significant correlations were found between these cytokines and protease activity. This study identifies several crucial markers for further researches on the molecular basis of AAA.


2015 ◽  
Vol 26 (7) ◽  
pp. 2378-2386 ◽  
Author(s):  
Alain Nchimi ◽  
Audrey Courtois ◽  
Mounia El Hachemi ◽  
Ziad Touat ◽  
Pierre Drion ◽  
...  

2009 ◽  
Vol 12 (1) ◽  
pp. 73-81 ◽  
Author(s):  
Danny Bluestein ◽  
Kris Dumont ◽  
Matthieu De Beule ◽  
John Ricotta ◽  
Paul Impellizzeri ◽  
...  

Author(s):  
Florentina Ene ◽  
Carine Gachon ◽  
Patrick Delassus ◽  
Liam Morris

Abdominal aortic aneurysm (AAA) represents an abnormal dilatation and weakening of the abdominal aorta with high risk of rupture. Most aneurysms of the infrarenal aorta possess an asymmetrical fusiform morphology.


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