Epigenetic Profiling Identifies Novel Genes for Ascending Aortic Aneurysm Formation with Bicuspid Aortic Valves

2015 ◽  
Vol 18 (4) ◽  
pp. 134 ◽  
Author(s):  
Asad A Shah
Keyword(s):  
Gene Expression ◽  
Aortic Aneurysm ◽  
Methylation Status ◽  
Aortic Aneurysms ◽  
Aortic Valves ◽  
Ascending Aortic Aneurysm ◽  
Novel Genes ◽  
Aneurysm Formation ◽  
Aortic Replacement ◽  
Bicuspid Aortic Valves

<p><strong>Background:  </strong>Bicuspid aortic valves predispose to ascending aortic aneurysms, but the mechanisms underlying this aortopathy remain incompletely characterized.  We sought to identify epigenetic pathways predisposing to aneurysm formation in bicuspid patients.</p><p><strong>Methods:  </strong>Ascending aortic aneurysm tissue samples were collected at the time of aortic replacement in subjects with bicuspid and trileaflet aortic valves.  Genome-wide DNA methylation status was determined on DNA from tissue using the Illumina 450K methylation chip, and gene expression was profiled on the same samples using Illumina Whole-Genome DASL arrays.  Gene methylation and expression were compared between bicuspid and trileaflet individuals using an unadjusted Wilcoxon rank sum test.  </p><p><strong>Results:  </strong>Twenty-seven probes in 9 genes showed significant differential methylation and expression (P&lt;5.5x10<sup>-4</sup>).  The top gene was protein tyrosine phosphatase, non-receptor type 22 (<em>PTPN22</em>), which was hypermethylated (delta beta range: +15.4 to +16.0%) and underexpressed (log 2 gene expression intensity: bicuspid 5.1 vs. trileaflet 7.9, P=2x10<sup>-5</sup>) in bicuspid patients, as compared to tricuspid patients.  Numerous genes involved in cardiovascular development were also differentially methylated, but not differentially expressed, including <em>ACTA2</em> (4 probes, delta beta range:  -10.0 to -22.9%), which when mutated causes the syndrome of familial thoracic aortic aneurysms and dissections</p><p><strong>Conclusions:  </strong>Using an integrated, unbiased genomic approach, we have identified novel genes associated with ascending aortic aneurysms in patients with bicuspid aortic valves, modulated through epigenetic mechanisms.  The top gene was <em>PTPN22</em>, which is involved in T-cell receptor signaling and associated with various immune disorders.  These differences highlight novel potential mechanisms of aneurysm development in the bicuspid population.</p>

scholarly journals Mesenchymal state of intimal cells may explain higher propensity to ascending aortic aneurysm in bicuspid aortic valves

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Shohreh Maleki ◽  
◽  
Sanela Kjellqvist ◽  
Valentina Paloschi ◽  
Joelle Magné ◽  
...  
Keyword(s):  
Aortic Aneurysm ◽  
Aortic Valves ◽  
Ascending Aortic Aneurysm ◽  
Bicuspid Aortic Valves

scholarly journals Management of bicuspid aortic valves in patients having repair or replacement of ascending aortic aneurysm

2003 ◽  
Vol 41 (6) ◽  
pp. 477
Author(s):  
Gruschen R. Veldtman ◽  
Heidi M. Connolly ◽  
Thomas A. Orszulak ◽  
Joseph A. Dearani ◽  
Hartzell V. Schaff
Keyword(s):  
Aortic Aneurysm ◽  
Aortic Valves ◽  
Ascending Aortic Aneurysm ◽  
Bicuspid Aortic Valves

scholarly journals A 60-year-old woman with asymptomatic total thoracic–abdominal aortic aneurysm

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Jianying Deng ◽  
Wei Liu
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Effective Treatment ◽  
Clinical Symptoms ◽  
Aortic Aneurysms ◽  
Case Presentation ◽  
Second Stage ◽  
Aortic Replacement ◽  
Abdominal Aortic ◽  
Thoracoabdominal Aortic Replacement

Abstract Introduction Total thoracic–abdominal aortic aneurysm is a rare disease in cardiovascular surgery, with high surgical risk and high mortality. Surgery is considered the most effective treatment for total aortic aneurysms. Case presentation Our group admitted a 60-year-old female patients with asymptomatic complex total thoracic–abdominal aortic aneurysm, and successfully performed two-staged surgery, namely Bentall + Sun’s operation in the first-stage and thoracoabdominal aortic replacement in the second-stage. The results of the surgery were satisfactory. Conclusions Patients with total thoracic–abdominal aortic aneurysm may not have typical clinical symptoms and require a careful and comprehensive physical examination and related auxiliary examinations by clinicians. Staged repair of total thoracic–abdominal aortic aneurysms is still a safe and effective treatment.

Abstract TP86: Prevalence of Bicuspid Aortic Valves and Thoracic Ascending Aortic Aneurysms in Patients Treated for Intracranial Aneurysms

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Manu S Goyal ◽  
Ravi Gottumukkala ◽  
Sanjeev Bhalla ◽  
Andrew M Kates ◽  
Gregory J Zipfel ◽  
...  
Keyword(s):  
Intracranial Aneurysms ◽  
Aortic Aneurysms ◽  
Chest Imaging ◽  
Aortic Valves ◽  
Cross Sectional ◽  
Population Prevalence ◽  
Prevalence Estimates ◽  
Bicuspid Aortic Valves ◽  
And Gender ◽  
Clinical Records

INTRODUCTION: Prior studies have suggested an increased prevalence of intracranial aneurysms (ICA) in patients with bicuspid aortic valves (BAV) and thoracic ascending aortic aneurysms (TAA). We tested the hypothesis that if true, conversely, the prevalence of BAV and TAA should be increased in patients with ICA. METHODS: We identified and reviewed the clinical records of patients treated for an ICA at our institution between 2002 and 2011. Only those with an echocardiogram report in their clinical record were included for further analysis. The prevalence of BAV and TAA in this cohort was determined based on the echocardiogram reports, medical records, and, when available, cross-sectional chest imaging. Proportion confidence intervals were calculated and compared to population prevalence estimates. RESULTS: Of 1051 patients with ICA, 321 had available echocardiogram reports that included assessment of the aortic valve. Of these, 85 also had cross-sectional chest imaging. Of the 321 patients, 2 were reported to have a BAV (0.6%, 95% CI 0 - 2.5%), similar to population prevalence estimates for this condition. In this same cohort, there were 15 (4.7%, 95% CI 2.7 - 7.8%) patients with a TAA. Among the 85 patients with cross-sectional chest imaging, the prevalence of TAA exceeded that expected for a community age- and gender-matched population (see Figure, gray lines represent upper and lower limits of normal). CONCLUSIONS: This retrospective analysis suggests an increased prevalence of TAA, but not BAV, in patients with ICA.

711 Novel gene expression changes in bicuspid aortic valves

2011 ◽  
Vol 27 (5) ◽  
pp. S324
Author(s):  
B. Yanagawa ◽  
F. Lovren ◽  
M. Peterson ◽  
A. Quan ◽  
L. Errett ◽  
...  
Keyword(s):  
Gene Expression ◽  
Aortic Valves ◽  
Novel Gene ◽  
Bicuspid Aortic Valves

scholarly journals Natural History of Ascending Aortic Aneurysms (40-50 mm): Impact of Bicuspid Aortic Valves

2020 ◽  
Author(s):  
Tarek Malas ◽  
Eric Dumont ◽  
Siamak Mohammadi ◽  
Pierre Voisine ◽  
François Dagenais
Keyword(s):  
Natural History ◽  
Aortic Aneurysms ◽  
Aortic Valves ◽  
Bicuspid Aortic Valves ◽  
History Of

scholarly journals Engineering Analysis of Aortic Wall Stress in the Surgery of V-shape Resection of the Noncoronary Sinus

2020 ◽  
Author(s):  
Hai Dong ◽  
Minliang Liu ◽  
Tongran Qin ◽  
Liang Liang ◽  
Bulat Ziganshin ◽  
...  
Keyword(s):  
Aortic Aneurysm ◽  
Stress Field ◽  
Aortic Arch ◽  
Aortic Root ◽  
Wall Stress ◽  
Aortic Aneurysms ◽  
Patient Specific ◽  
Rupture Risk ◽  
Ascending Aortic Aneurysm ◽  
Post Surgery

AbstractAscending aortic aneurysms often include the sinotubular junction (STJ) and extend into the root portion of the aorta. The novel surgery of the V-shape resection of the noncoronary sinus of the aortic root has been shown to be a simpler procedure, comparing with traditional surgeries such as full aortic root replacement, for patients with moderate ascending aortic aneurysm and aortic root ectasia. This novel surgery could reduce the diameter and cross-sectional area of the aortic root. However, the detailed effect on the stress field and the rupture risk of the aortic root and aneurysm has not been fully investigated. In this study, we performed patient-specific finite element (FE) analysis based on the 3D geometries of the aortic root and ascending aortic aneurysm, reconstructed directly from the clinical computed tomographic (CT) images. By comparing the pre- and post-surgery results, we investigated the influence of the V-shape surgery on the stress field and rupture risk of the aortic root, ascending aortic aneurysm and aortic arch. It was found that the surgery could significantly reduce the wall stress of the aortic root, ascending aortic aneurysm, as well the aortic arch, and hence lower the rupture risk.

scholarly journals Ascending aortic aneurysm: propensity score matching analysis of hemiarch and non-hemiarch replacement

2020 ◽  
Vol 25 (10) ◽  
pp. 3887
Author(s):  
B. N. Kozlov ◽  
D. S. Panfilov ◽  
E. L. Sonduev ◽  
V. L. Lukinov
Keyword(s):  
Myocardial Infarction ◽  
Aortic Aneurysm ◽  
Propensity Score ◽  
Hospital Mortality ◽  
Propensity Score Matching ◽  
Ascending Aortic Aneurysm ◽  
Aortic Replacement ◽  
Prolonged Ventilation ◽  
Ascending Aortic Replacement ◽  
Hemiarch Replacement

Aim. To compare the shortand medium-term outcomes of hemiarch and nonhemiarch replacement for ascending aortic aneurysm (AAA).Material and methods. The study included 151 patients with non-syndromic AAA who underwent an elective replacement. Patients were divided into two groups: group 1 (non-hemiarch, n=40) — standard ascending aortic replacement; group 2 (hemiarch, n=111) — ascending aortic replacement with the hemiarch anastomosis in conditions of moderate hypothermia and circulatory arrest with unilateral antegrade cerebral perfusion. To eliminate systematic differences between the compared groups, the propensity score matching (PSM) method was used.Results. Before PSM, there were no significant intergroup differences in the incidence of neurological complications, myocardial infarction, prolonged ventilation, or acute kidney injury. Bleeding-related reoperation rates and hospital mortality significantly differed between groups. After pseudo-randomization between the non-hemiarch and hemiarch groups, there were no significant differences in the incidence of neurological events, myocardial infarction, prolonged ventilation, reoperations for bleeding, acute renal injury, and hospital mortality. Median-term survival and freedom from aortic reoperations also did not show significant intergroup differences.Conclusion. Hemiarch replacement for AAA does not lead to an increase in the incidence of postoperative complications, as well as the risk of shortand mediumterm mortality compared with non-hemiarch.

scholarly journals Inflammation and TGF-β Signaling Differ between Abdominal Aneurysms and Occlusive Disease

2019 ◽  
Vol 6 (4) ◽  
pp. 38 ◽  
Author(s):  
IJpma ◽  
te Riet ◽  
van de Luijtgaarden ◽  
van Heijningen ◽  
Burger ◽  
...  
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Expression Profiles ◽  
Gene List ◽  
Occlusive Disease ◽  
Aortic Aneurysms ◽  
Pharmacological Intervention ◽  
Novel Genes ◽  
Abdominal Aortic

Abdominal aortic aneurysms (AAA), are usually asymptomatic until rupture causes fatal bleeding, posing a major vascular health problem. AAAs are associated with advanced age, male gender, and cardiovascular risk factors (e.g. hypertension and smoking). Strikingly, AAA and AOD (arterial occlusive disease) patients have a similar atherosclerotic burden, yet develop either arterial dilatation or occlusion, respectively. The molecular mechanisms underlying this diversion are yet unknown. As this knowledge could improve AAA treatment strategies, we aimed to identify genes and signaling pathways involved. We compared RNA expression profiles of abdominal aortic AAA and AOD patient samples. Based on differential gene expression profiles, we selected a gene set that could serve as blood biomarker or as pharmacological intervention target for AAA. In this AAA gene list we identified previously AAA-associated genes COL11A1, ADIPOQ, and LPL, thus validating our approach as well as novel genes; CXCL13, SLC7A5, FDC-SP not previously linked to aneurysmal disease. Pathway analysis revealed overrepresentation of significantly altered immune-related pathways between AAA and AOD. Additionally, we found bone morphogenetic protein (BMP) signaling inhibition simultaneous with activation of transforming growth factor β (TGF-β) signaling associated with AAA. Concluding our gene expression profiling approach identifies novel genes and an interplay between BMP and TGF-β signaling regulation specifically for AAA.

P3112The oral administration of colchicine prevents the progression of aortic aneurysm

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
H Okawa ◽  
A Yamawaki-Ogata ◽  
Y Narita ◽  
H Munakata ◽  
R Hashizume ◽  
...  
Keyword(s):  
Gene Expression ◽  
Aortic Aneurysm ◽  
Oral Administration ◽  
Inflammatory Cytokines ◽  
Nlrp3 Inflammasome ◽  
Aortic Aneurysms ◽  
Aortic Diameter ◽  
Tnf Α

Abstract Objective The pathogenesis of aortic aneurysm (AA) is characterized by the chronic inflammation of the aortic wall with the accumulation of macrophages and the degradation of the extracellular matrix (ECM) including elastin. Colchicine (COL) is an alkaloid derived from the plant Lily family Colchicum autumnale, and it is known for anti-inflammatory effects. Plant extracts containing COL have been used in the treatment of gout from ancient period. Currently, pseudogout, familial Mediterranean fever, Behçet's disease and pericarditis are also treated by COL. Furthermore, recent evidence suggests the use of COL for secondary prevention of cardiovascular disease, and the phase 3 clinical trial for it has begun. The objective of this study is to investigate whether COL could prevent the progression of aortic aneurysms. Methods In vitro: Macrophages (J774A.1 cell line) stimulated TNF-α 24 hours before and smooth muscle cell (SMC) were cultured with 10 ng/mL COL, and the gene expression of inflammatory cytokines involved in the AA formation was measured 24 hours later. In vivo: Male apolipoprotein E-deficient mice (30–35 weeks of age) were infused with angiotensin II for 28 days. COL (20 μg/kg/d) or saline (NS, as a control) was administered orally to the mice every day (COL group, n=8; NS group, n=8). Aortic diameter was measured by echography every week and all mice were sacrificed and their thoracoabdominal aorta was harvested at the last day of the administration period and elastin content, MMP activitis, and levels of inflammatory cytokines involved in the AA formation were measured. Results In vitro: The gene expression of IL-1β, TNF-α, MCP-1, NF-κB, MMP-9 in the macrophages was significantly decreased in the COL group. The gene expression of Lox, TIMP-2 in the SMC were significantly increased in COL group. In vivo: Aortic diameter measured by echography every week was significantly suppressed in the COL group (2.25 vs 2.81 mm, p<0.05). The incidence of AA was decreased in the COL group (62.5% vs 100%). COL significantly suppressed the degeneration of aortic elastin in EVG staining (p<0.05). There is no significant difference in the enzyme activities of MMP-2 and MMP-9 between COL and NS groups, but IL-1β (54.4 vs 81.4, p<0.05), TNF-α (31.0 vs 60.6, p<0.05), MCP-1 (258.2 vs 411.2, p<0.05), NLRP3 inflammasome (7.1 vs 8.6, p<0.05), NE (1.5 vs 2.4, p<0.05), MPO (44.9 vs 48.1, p<0.05) were decreased in the COL group. Discussion In AA model mice, COL seems to suppress the progression of AA by anti-infammation and preservation of the ECM structure through the inhibition of NLRP3 inflammasome. That NLRP3 inflammasome activation leads to the progression of AA in AA model mice was previously reported and this supports out results. Methods and Results (in vivo) Conclusions This results suggest that the oral administration of COL prevents the progression of AA in AA model mice and it is expected as a novel therapeutic agent for AA. Acknowledgement/Funding JSPS KAKENHI Grant

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