scholarly journals Identification of Novel microRNA Profiles Dysregulated in Plasma and Tissue of Abdominal Aortic Aneurysm Patients

2020 ◽  
Vol 21 (13) ◽  
pp. 4600 ◽  
Author(s):  
Emma Plana ◽  
Laura Gálvez ◽  
Pilar Medina ◽  
Silvia Navarro ◽  
Victoria Fornés-Ferrer ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Aortic Tissue ◽  
Tissue Samples ◽  
Entire Study ◽  
Abdominal Aortic ◽  
Study Population ◽  
Interaction Map

microRNAs (miRNAs) are small RNAs that regulate different biological processes. Our objective was to identify miRNAs dysregulated in plasma and tissue of patients with abdominal aortic aneurysm (AAA) and explore new potential targets involved in AAA. Fifty-seven subjects were recruited for a plasma study (30 AAA patients, 16 healthy volunteers and 11 patients with atherosclerosis). The expression level of 179 miRNAs was screened in plasma from a subset of samples, and dysregulated miRNAs were validated in the entire study population. Dysregulated miRNAs were also quantified in aortic tissue of 21 AAA patients and 8 organ donors. Applying a gene set enrichment analysis, an interaction map of dysregulated miRNAs and their targets was built, and selected targets were quantified in tissue samples. miR-27b-3p and miR-221-3p were overexpressed in plasma of AAA patients compared with healthy controls, 1.6 times and 1.9 times, respectively. In AAA tissue, six miRNAs (miR-1, miR-27b-3p, miR-29b-3p, miR-133a-3p, miR-133b, and miR-195-5p) were underexpressed from 1.6 to 4.8 times and four miRNAs (miR-146a-5p, miR-21-5p, miR-144-3p, and miR-103a-3p) were overexpressed from 1.3 to 7.2 times. Thrombospondin-2, a target of miR-195-5p, was increased in AAA tissue and negatively correlated with the expression of miR-195-5p, suggesting their involvement in a common regulatory mechanism.

scholarly journals Swedish snuff (snus) and risk of cardiovascular disease and mortality: prospective cohort study of middle-aged and older individuals

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Olga E. Titova ◽  
John A. Baron ◽  
Karl Michaëlsson ◽  
Susanna C. Larsson
Keyword(s):  
Cardiovascular Disease ◽  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Older Individuals ◽  
Middle Aged ◽  
Entire Study ◽  
Abdominal Aortic ◽  
Increased Risk ◽  
Never Smokers ◽  
Cvd Mortality

Abstract Background Cigarette smoking is a well-known risk factor for cardiovascular disease (CVD), but whether smokeless tobacco such as snuff is associated with the risk of CVD is still unclear. We investigated the association of the use of Swedish oral moist snuff (snus) with a broad range of CVDs and CVD mortality. Methods We used data from a population-based cohort of 41,162 Swedish adults with a mean baseline age of 70 (56–94) years who completed questionnaires regarding snus use and other lifestyle habits and health characteristics. Participants were followed up for incident cardiovascular outcomes and death over 8 years through linkage to the Swedish National Patient and Death Registers. Hazard ratios (HR) were estimated by Cox proportional hazards regression. We conducted analyses among all subjects as well as among never smokers to reduce residual confounding from smoking. Results After adjustment for smoking and other confounders, snus use was not associated with myocardial infarction, heart failure, atrial fibrillation, aortic valve stenosis, abdominal aortic aneurysm, stroke, or CVD mortality. However, in never smokers, snus use was associated with a statistically significant increased risk of total and ischemic stroke (HRs [95% confidence intervals] = 1.52 [1.01–2.30] and 1.63 [1.05–2.54], respectively) and non-significantly positively associated with some other CVDs. Conclusions In this middle-aged and elderly Swedish population, current Swedish snus use was not associated with the risk of major heart and valvular diseases, abdominal aortic aneurysm, or CVD mortality in the entire study population, but was linked to an increased risk of stroke in never smokers.

scholarly journals Discovery of crucial cytokines associated with abdominal aortic aneurysm formation by protein array analysis

2019 ◽  
Vol 244 (18) ◽  
pp. 1648-1657
Author(s):  
Yuan Li ◽  
Dan Yang ◽  
Bo Sun ◽  
Xu Zhang ◽  
Fangda Li ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Cathepsin L ◽  
Enrichment Analysis ◽  
Differentially Expressed ◽  
Antibody Array ◽  
Pathway Enrichment Analysis ◽  
Pathway Enrichment ◽  
Abdominal Aortic ◽  
Related Proteins

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.

Prevalence of Renal Masses Suspected of Malignancy and Adrenal Incidentalomas in Patients With Abdominal Aortic Aneurysm

2021 ◽  
pp. 153857442110226
Author(s):  
Dorota Studzińska ◽  
Mateusz Kózka ◽  
Kamil Polok ◽  
Katarzyna Gronostaj ◽  
Maciej Chwała ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Abdominal Aortic Aneurysms ◽  
Aortic Aneurysms ◽  
Renal Tumors ◽  
Type Ii ◽  
Adrenal Incidentalomas ◽  
Renal Masses ◽  
Abdominal Aortic ◽  
Study Population

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.

Results of Autopsy 7 Months after Successful Endoluminal Treatment of an Infrarenal Abdominal Aortic Aneurysm

1995 ◽  
Vol 2 (4) ◽  
pp. 348-355 ◽  
Author(s):  
Timothy J. McGahan ◽  
Gerald A. Berry ◽  
Sarah L. McGahan ◽  
Geoffrey H. White ◽  
Weiyun Yu ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Microscopic Examination ◽  
Aortic Wall ◽  
Aortic Tissue ◽  
Esophageal Rupture ◽  
Spontaneous Esophageal Rupture ◽  
Infrarenal Abdominal Aortic Aneurysm ◽  
Abdominal Aortic ◽  
Endoluminal Treatment

Purpose: To report the results of a postmortem examination in a patient who died of unrelated causes 7 months following endoluminal treatment of an infrarenal abdominal aortic aneurysm (AAA). Methods: As part of an FDA Phase I pilot study, a 73-year-old man underwent successful endoluminal exclusion of an infrarenal AAA using a 9-cm-long endograft (Endovascular Grafting System). Seven months later, he succumbed to complications of a spontaneous esophageal rupture. At autopsy, the aorta was dissected in situ by a vascular surgeon and pathologist before being explanted in order to examine the wound healing characteristics at the aorta-endograft interface. Particular attention was also directed to the hooks composing the attachment system at each end of the endograft. Results: Macroscopic and microscopic examination revealed that the graft had completely excluded the aneurysm sac from the circulation and was incorporated into the aortic wall at the proximal neck and distal cuff. A smooth pannus of endothelial cells covered the proximal end of the endograft at the areas of contact with the aorta, while microscopic examination of the distal end of the graft revealed poorly formed, fibrinous pannus. The neointima deep to the endothelium consisted of a collagenous matrix containing myofibroblasts and histiocytes, providing evidence of healing between the endograft and aorta. Both renal arteries were clear of the proximal end of the endograft, but a previously unrecognized right lower pole renal artery with an extremely caudal origin was excluded from the aortic lumen. Each hook of the attachment system was seen protruding through the adventitia of the aorta. There was no evidence of trauma to the aortic wall or the surrounding tissues caused by these hooks. Conclusion: There appears to be evidence that an endoluminally placed aortic graft may be incorporated by the host aortic tissue.

Comparison of Efficacy between Ramipril and Carvedilol on Limiting the Expansion of Abdominal Aortic Aneurysm in Mouse Model

2018 ◽  
Vol 24 (2) ◽  
pp. 172-181 ◽  
Author(s):  
Sang Min Park ◽  
Myeong-Ki Hong ◽  
Se Hoon Kim ◽  
Subin Jung ◽  
Bo Kyoung Kim ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Mouse Model ◽  
Similar Efficacy ◽  
Saline Group ◽  
Aortic Tissue ◽  
Micro Computed Tomography ◽  
Monocyte Chemoattractant Protein 1 ◽  
Matrix Metalloproteinase 1 ◽  
Abdominal Aortic

Objective: Abdominal aortic aneurysm (AAA) is a common condition that may be life-threatening when it is unrecognized. The aim of this study is to evaluate and compare the efficacy of ramipril and carvedilol on limiting AAA expansion in mouse model. Methods and Results: A total of 36 experimental AAA mouse model was induced with the continuous infusion of angiotensin II (Ang II) in 20-week-old male apolipoprotein E-deficient mice. They were randomly divided into 3 treatment groups and fed orally for 8 weeks; saline alone, ramipril (2.5 mg/30g/d), or carvedilol (3.125 mg/30g/d), respectively. Aortic diameter (AD) was measured by micro-computed tomography, and the level of biomarkers of aortic tissue such as monocyte chemoattractant protein-1 (MCP-1) and tissue inhibitor matrix metalloproteinase-1 (TIMP-1) was evaluated. After treatment, AD of both ramipril and carvedilol group was smaller than in the saline group. The percentage change of AD in both ramipril and carvedilol groups was significantly smaller than that of the saline group. Pathologic examination revealed relatively well-preserved aortic walls in the ramipril group compared to the carvedilol and saline groups. The level of MCP-1 was markedly decreased in both the ramipril and carvedilol groups compared to the saline group. The level of TIMP-1 was higher in the carvedilol group when compared to either the saline or ramipril groups. Conclusions: Ramipril and carvedilol treatment shows similar efficacy in limiting AAA expansion in mouse model. Future clinical research would be warranted to validate these results.

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.

Abstract 255: Induction of microRNA-21 Inhibits Abdominal Aortic Aneurysm Development and Nicotine-Augmented Expansion

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Lars Maegdefessel ◽  
Junya Azuma ◽  
Ryuji Toh ◽  
Alicia Deng ◽  
Denis Merk ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Therapeutic Option ◽  
Locked Nucleic Acid ◽  
Aortic Tissue ◽  
Protective Effects ◽  
Vascular Medicine ◽  
Apoptotic Pathway ◽  
Systemic Injection ◽  
Abdominal Aortic

Identification and treatment of abdominal aortic aneurysm (AAA) remain among the most prominent challenges in vascular medicine. MicroRNAs (miRs) are crucial regulators of cardiovascular pathology, and represent possible targets for the inhibition of AAA expansion. We identified miR-21 as a key modulator of proliferation and apoptosis in developing AAA in two established murine models: porcine-pancreatic-elastase, and angiotensin II-infusion. In both models, miR-21 increased with AAA development. Lentiviral overexpression of miR-21 (pre-21) induced cell proliferation and decreased apoptosis in the aortic wall, with protective effects on aneurysm expansion (as shown in Picrosirius Red stained images in the attached Figure below). miR-21 overexpression substantially decreased phosphatase and tensin homolog (PTEN), leading to increased levels of p-AKT, a known pro-proliferative and anti-apoptotic pathway. Systemic injection of a locked-nucleic-acid-modified antagomiR targeting miR-21 (anti-21) diminished the pro-proliferative impact of down-regulated PTEN, leading to significantly increased AAA size as compared to scrambled-control-miR (scr-miR). Importantly, similar results were seen in nicotine-augmented murine AAAs, while parallel findings were observed in human aortic tissue samples from patients undergoing surgical AAA repair (with more pronounced effects in smokers). In vitro studies using human aortic smooth muscle cells, fibroblasts as well as endothelial cells identified NFκB signaling pathways as the key regulator of miR-21 induction. Modulation of miR-21 expression shows great potential as a novel and powerful therapeutic option to limit AAA disease progression.

Automated Methodology for Determination of Stress Distribution in Human Abdominal Aortic Aneurysm

2005 ◽  
Vol 127 (5) ◽  
pp. 868-871 ◽  
Author(s):  
Madhavan L. Raghavan ◽  
Mark F. Fillinger ◽  
Steven P. Marra ◽  
Bernhard P. Naegelein ◽  
Francis E. Kennedy
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Peak Stress ◽  
Wall Stress ◽  
Patient Specific ◽  
Element Analysis ◽  
Biomechanical Stress ◽  
Abdominal Aortic ◽  
Study Population ◽  
Peak Wall Stress

Knowledge of impending abdominal aortic aneurysm (AAA) rupture can help in surgical planning. Typically, aneurysm diameter is used as the indicator of rupture, but recent studies have hypothesized that pressure-induced biomechanical stress may be a better predictor. Verification of this hypothesis on a large study population with ruptured and unruptured AAA is vital if stress is to be reliably used as a clinical prognosticator for AAA rupture risk. We have developed an automated algorithm to calculate the peak stress in patient-specific AAA models. The algorithm contains a mesh refinement module, finite element analysis module, and a postprocessing visualization module. Several aspects of the methodology used are an improvement over past reported approaches. The entire analysis may be run from a single command and is completed in less than 1h with the peak wall stress recorded for statistical analysis. We have used our algorithm for stress analysis of numerous ruptured and unruptured AAA models and report some of our results here. By current estimates, peak stress in the aortic wall appears to be a better predictor of rupture than AAA diameter. Further use of our algorithm is ongoing on larger study populations to convincingly verify these findings.

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 Cyclophilin A/EMMPRIN Axis Is Involved in Pro-Fibrotic Processes Associated with Thoracic Aortic Aneurysm of Marfan Syndrome Patients

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 154 ◽  
Author(s):  
Gianluca L. Perrucci ◽  
Erica Rurali ◽  
Maria Corlianò ◽  
Maria Balzo ◽  
Michela Piccoli ◽  
...  
Keyword(s):  
Aortic Aneurysm ◽  
Marfan Syndrome ◽  
Thoracic Aortic Aneurysm ◽  
Cyclophilin A ◽  
Aortic Tissue ◽  
Tissue Samples ◽  
Abdominal Aortic ◽  
Tgf Β1 ◽  
In Vitro Treatment

Background: Marfan syndrome (MFS) is a genetic disease, characterized by thoracic aortic aneurysm (TAA), which treatment is to date purely surgical. Understanding of novel molecular targets is mandatory to unveil effective pharmacological approaches. Cyclophilin A (CyPA) and its receptor EMMPRIN are associated with several cardiovascular diseases, including abdominal aortic aneurysm. Here, we envisioned the contribution of CyPA/EMMPRIN axis in MFS-related TAA. Methods: We obtained thoracic aortic samples from healthy controls (HC) and MFS patients’ aortas and then isolated vascular smooth muscle cells (VSMC) from the aortic wall. Results: our findings revealed that MFS aortic tissue samples isolated from the dilated zone of aorta showed higher expression levels of EMMPRIN vs. MFS non-dilated aorta and HC. Interestingly, angiotensin II significantly stimulated CyPA secretion in MFS-derived VSMC (MFS-VSMC). CyPA treatment on MFS-VSMC led to increased levels of EMMPRIN and other MFS-associated pro-fibrotic mediators, such as TGF-β1 and collagen I. These molecules were downregulated by in vitro treatment with CyPA inhibitor MM284. Our results suggest that CyPA/EMMPRIN axis is involved in MFS-related TAA development, since EMMPRIN is upregulated in the dilated zone of MFS patients’ TAA and the inhibition of its ligand, CyPA, downregulated EMMPRIN and MFS-related markers in MFS-VSMC. Conclusions: these insights suggest both a novel detrimental role for CyPA/EMMPRIN axis and its inhibition as a potential therapeutic strategy for MFS-related TAA treatment.

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