Abstract 284: microRNAs are Novel Plasma Biomarkers for Diagnosis and Prognosis of Abdominal Aortic Aneurysm Disease

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Ekaterina Chernogubova ◽  
Suzanne M Eken ◽  
Hong Jin ◽  
Joy Roy ◽  
Anders Hamsten ◽  
...  
Keyword(s):  
Prognostic Value ◽  
Aortic Aneurysms ◽  
Control Group ◽  
Aortic Tissue ◽  
Plasma Samples ◽  
Diagnosis And Prognosis ◽  
Abdominal Aortic ◽  
Increased Risk ◽  
Fine Tune ◽  
Pump Implantation

MicroRNAs (miRNAs) have been identified as transcriptional and posttranscriptional inhibitors of gene expression, thought to “fine tune” the translational output of their target mRNAs. Recently, they have received much attention regarding their suitability as biomarkers for disease. Our goal was to explore the diagnostic and prognostic value of miRNAs in abdominal aortic aneurysms (AAAs), a disease for which currently no established biomarker exists. Using a PCR-based array platform, we profiled the 168 most abundant blood miRNAs in 20 patient plasma samples with AAA disease, undergoing surgical repair of their enlarged aorta vs. 20 samples from an age, risk factor, and medication matched control group without aneurysm. We were able to identify a total number of 12 miRNAs being significantly altered in diseased patient samples as compared to controls. We further investigated these 12 miRNAs in plasma (as well as in aortic tissue) from apoE-/- mice with angiotensinII (AngII)-infusion induced AAAs, enabling us to discover a potential prognostic value of miRNAs being released into circulation. Indeed we were able to detect that the expression of 4 out of the 12 miRNAs (miRs-126 and -668 both increased; miRs-24 and -210 both decreased), was substantially modified in plasma samples drawn from mice with AAA immediately before rupture occurred between days 10 and 14 after AngII pump implantation compared to mice with AAA that did not rupture for the remainder of study (28 days), as well as saline-infused controls. Importantly, the expression of miRs-24 and -126 appeared also significantly different in plasma samples from patients with ruptured AAAs (n=7) compared to patients with non-ruptured AAAs (abdominal aortic diameter between 55-78 mm; n=7) and un-diseased controls (n=7). The present study explores the diagnostic and prognostic biomarker potential of miRNAs being released into circulation during initiation, propagation, and ultimately rupture of AAA disease in mice and humans. The identification of miRs-24, -126, -210, and -663 potentially offers great prognostic value to determine which patients present with an increased risk of AAA rupture.

Abstract 108: Diagnostic and Prognostic Biomarker Potential of miR-24 in Abdominal Aortic Aneurysm Disease and Rupture

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Ekaterina Chernogubova ◽  
Suzanne Eken ◽  
Joshua Spin ◽  
Hong Jin ◽  
Uwe Raaz ◽  
...  
Keyword(s):  
Prognostic Value ◽  
Surgical Repair ◽  
Aortic Rupture ◽  
Aortic Aneurysms ◽  
Plasma Samples ◽  
Abdominal Aortic ◽  
Increased Risk ◽  
Circulating Levels ◽  
Pump Implantation ◽  
Diagnostic And Prognostic Value

MicroRNAs (miRNAs) have lately received much attention regarding their suitability and feasibility as biomarkers for cardiovascular diseases. Aim of this current study was to explore the diagnostic and prognostic value of detecting circulating levels of miRNAs in abdominal aortic aneurysms (AAAs). Using a PCR-based array, we profiled the 168 most abundant blood miRNAs in 20 patient plasma samples with AAA disease, undergoing surgical repair of their enlarged aorta vs. 20 samples from a matched screening cohort without aneurysm. We were able to identify a total number of 12 miRNAs that were significantly altered in diseased patient samples as compared to controls. Next we investigated these 12 miRNAs in plasma from ApoE-/- mice with angiotensinII (AngII)-infusion induced AAAs, in order to determine the potential prognostic value of miRNAs being released into circulation. Indeed we were able to detect that the expression of 4 out of the 12 miRNAs (miRs-126 and -668 both increased; miRs-24 and -210 both decreased), was substantially altered in plasma samples drawn from AAA mice immediately before rupture occurred between days 10 and 14 after AngII pump implantation compared to mice with AAA that did not rupture for the remainder of study (28 days), as well as saline-infused controls. The expression of miR-24 was furthermore significantly different in plasma samples from human patients with acutely ruptured AAAs (n=7) compared to patients with non-ruptured AAAs (AA diameter between 55-78 mm; n=7) undergoing surgical repair, as well as un-diseased controls (n=7). Using the AngII model, as well as the elastase infusion model, we were able to show that overexpression of miR-24 protects from aneurysm progression as well as aortic rupture (in the AngII model) by repressing the expression of its target gene chitinase3-like1 (Chi3l1), which regulates macrophage survival and cytokine release in expanding murine AAAs. The present study explores the biomarker potential of miRNAs being released into circulation during initiation, propagation, and ultimately rupture of AAA disease in mice and humans. The identification of miR-24 potentially offers prognostic value to determine which patients present with increased risk of rapid AAA expansion and subsequent rupture.

scholarly journals Integrated Plasma and Tissue Proteomics Reveals Attractin Release by Intraluminal Thrombus of Abdominal Aortic Aneurysms and Improves Aneurysm Growth Prediction in Humans

2020 ◽  
Author(s):  
Regent Lee ◽  
Ismail Cassimee ◽  
Honglei Huang ◽  
Pierfrancesco Lapolla ◽  
Anirudh Chandrashekar ◽  
...  
Keyword(s):  
Growth Rate ◽  
Endothelial Dysfunction ◽  
Abdominal Aortic Aneurysms ◽  
Aortic Aneurysms ◽  
Universal Method ◽  
Plasma Samples ◽  
Growth Prediction ◽  
Aneurysm Wall ◽  
Abdominal Aortic ◽  
Increased Risk

Background: Abdominal aortic aneurysms (AAA) are pathological dilatations of the aorta which can result in rupture and mortality. Novel methods of predicting AAA growth is a recognised priority in AAA research. Patient with AAAs have increased risk of cardiovascular morbidity. We have previously observed accelerated systemic endothelial dysfunction (measured by brachial artery FMD) in AAA patients and FMD correlates with future AAA growth. Further, systemic endothelial dysfunction is reversed by AAA repair. AAAs contain intra-luminal thrombus (ILT). Since ILT is either removed or excluded from circulation after successful repair of AAAs, we hypothesise that ILT to be the source of mediators that contribute to AAA growth. Methods: Patients were prospectively recruited to the Study (Ethics Ref SC/13/0250). Plasma samples were collected at baseline and at 1 year from each patient. Plasma samples were also collected before and at 10-12 weeks after surgery from each patient (n=29). Paired aneurysm wall, ILT, omental biopsies were collected intra-operatively during open surgical repair (n=3). In addition to analyses of the tissue, supernatant was obtained from ex vivo culture of these paired tissue samples. Samples were subjected to non-targeted LC-MSMS workflow after trypsin digest, using the Universal method to discover novel proteins. LC-MSMS data was analysed using the Progenesis QI pipeline. Results: The median AAA size at baseline was 48 mm. 59 patients were prospectively followed for 12 months. The median growth rate of AAA was 3.8%/year (IQR 1.9% to 6.8%). Comparison between patients with the fastest vs the slowest (n=10 each) showed 116 proteins to be differentially expressed in their plasma. Among these proteins, 35 also changed significantly before and after AAA repair, suggesting their origin to from the AAA complex. Comparison of the proteomics profile of aneurysm tissue, ILT, and omental artery show 128 proteins to be uniquely present in ILT. Analyses of the tissue culture supernatant further revealed 3 proteins that are: (i) uniquely present in ILT; (ii) released by ILT; (iii) systemic levels reduced after AAA surgery; (iv) differs between fast and slow growth AAAs. One of these proteins is attractin. To validate the LC-MSMS data, attractin level in individual patient was measured by ELISA. Consistent with the LC-MSMS data, plasma attractin level is higher in patients with fast AAA growth. Plasma attractin level correlates significantly with future AAA growth rate (Spearman r=0.35, P<;0.005). Using attractin and AAA diameter as input variables, the AUROC for predicting no growth of AAA at 12 months is 85% (P<0.001). Conclusion: We show that ILT of AAAs releases mediators (such as attractin) during the natural history of AAA growth. These are novel biomarkers for AAA growth prediction in humans.

scholarly journals The Prevalence of Concomitant Abdominal Aortic Aneurysm and Cancer

2021 ◽  
Vol 10 (17) ◽  
pp. 3847
Author(s):  
Hyangkyoung Kim ◽  
Sung-il Cho ◽  
Sungho Won ◽  
Youngjin Han ◽  
Tae-Won Kwon ◽  
...  
Keyword(s):  
Disease Process ◽  
Aortic Aneurysms ◽  
Secondary Outcome ◽  
Control Group ◽  
Control Groups ◽  
Term Survival ◽  
Abdominal Aortic ◽  
Increased Risk ◽  
And Control ◽  
Risk Of Cancer

Cancers and abdominal aortic aneurysms (AAA) cause substantial morbidity and mortality and commonly develop in old age. It has been previously reported that AAA patients have a high prevalence of cancers, which has raised the question of whether this is a simple collision, association or causation. Clinical trials or observational studies with sufficient power to prove this association between them were limited because of the relatively low frequency and slow disease process of both diseases. We aimed to determine whether there is a significant association between AAA and cancers using nationwide data. The patients aged > 50 years and diagnosed with AAA between 2002 and 2015, patients with heart failure (HF) and controls without an AAA or HF matched by age, sex and cardiovascular risk factors were enrolled from the national sample cohort from the National Health Insurance claims database of South Korea. The primary outcome was the prevalence rate of cancers in the participants with and without an AAA. The secondary outcome was cancer-related survival and cancer risk. Overall, 823 AAA patients (mean (standard deviation) age, 71.8 (9.4) years; 552 (67.1%) men) and matching 823 HF patients and 823 controls were identified. The prevalence of cancers was 45.2% (372/823), 41.7% (343/823) and 35.7% (294/823) in the AAA, HF and control groups, respectively; it was significantly higher in the AAA group than in the control group (p < 0.001). The risk of developing cancer was higher in the AAA patients than in the controls (adjusted odds ratio (OR), 1.52 (95% confidence interval [CI], 1.24–1.86), p < 0.001) and in the HF patients (adjusted OR, 1.37 (1.24–1.86), p = 0.006). The cancer-related death rate was 2.64 times higher (95% CI, 2.22–3.13; p < 0.001) for the AAA patients and 1.63 times higher (95% CI, 1.37–1.92; p < 0.001) for the HF patients than for the controls. The most common causes of death in the AAA patients were cancer and cardiovascular disease. There was a significantly increased risk of cancer in the AAA than in the HF and control groups. Therefore, appropriate screening algorithms might be necessary for earlier detection of both diseases to improve long-term survival.

Inflation Testing as a Means of Measuring Failure Strength of Aortic Tissue

2003 ◽  
Author(s):  
Jeffrey N. Kinkaid ◽  
Steven P. Marra ◽  
Francis E. Kennedy ◽  
Mark F. Fillinger
Keyword(s):  
United States ◽  
Abdominal Aortic Aneurysms ◽  
The United States ◽  
Aortic Aneurysms ◽  
Aortic Tissue ◽  
Failure Strength ◽  
Health Statistics ◽  
Mortality Risks ◽  
Abdominal Aortic ◽  
Risk Of Rupture

Abdominal Aortic Aneurysms (AAAs) are localized enlargements of the aorta. If untreated, AAAs will grow irreversibly until rupture occurs. Ruptured AAAs are usually fatal and are a leading cause of death in the United States, killing 15,000 per year (National Center for Health Statistics, 2001). Surgery to repair AAAs also carries mortality risks, so surgeons desire a reliable tool to evaluate the risk of rupture versus the risk of surgery.

scholarly journals Association of simple renal cysts and chronic kidney disease with large abdominal aortic aneurysm

2019 ◽  
Author(s):  
Milena Miszczuk ◽  
Verena Müller ◽  
Christian E. Althoff ◽  
Andrea Stroux ◽  
Daniela Widhalm ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Kidney Diseases ◽  
Strong Association ◽  
Renal Cysts ◽  
Aortic Aneurysms ◽  
Control Group ◽  
Abdominal Aortic ◽  
And Control ◽  
Charité Berlin

AbstractAbdominal aortic aneurysms (AAA) primarily affect elderly men who often have many other diseases, with similar risk factors and pathobiological mechanisms to AAA. The aim of this study was to assess the prevalence of simple renal cysts (SRC), chronic kidney disease (CKD), and other kidney diseases (e.g. nephrolithiasis) among patients presenting with AAA. Two groups of patients (100/group), with and without AAA, from the Surgical Clinic Charité, Berlin, Germany, were selected for the study. The control group consisted of patients who were evaluated for a kidney donation (n = 14) and patients who were evaluated for an early detection of a melanoma recurrence (n = 86). The AAA and control groups were matched for age and sex. Medical records were analyzed and computed tomography scans were reviewed for the presence of SRC and nephrolithiasis. SRC (73% vs. 57%; p<0.001) and CKD (31% vs. 8%; p<0.001) were both more common among AAA than control group patients. On multivariate analysis, CKD, but not SRC, showed a strong association with AAA. Knowledge about pathobiological mechanisms and association between CKD and AAA could provide better diagnostic and therapeutic approaches for these patients.

Abstract 919: Suppression of Abdominal Aortic Aneurysms in the Angiotensin II-infused ApoE Deficient Mice by Treatment with Chymase Inhibitor

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Nao Inoue ◽  
Michiko Muramatsu ◽  
Denan Jin ◽  
Shinji Takai ◽  
Tetsuya Hayashi ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Abdominal Aortic Aneurysms ◽  
Treated Group ◽  
Aortic Aneurysms ◽  
Aortic Diameter ◽  
Vehicle Group ◽  
Control Group ◽  
Abdominal Aortic ◽  
Chymase Inhibitor ◽  
Deficient Mice

Chymase promotes not only angiotensin II production but also matrix metalloproteinase (MMP)-9 activation, which have a critical role on development of abdominal aortic aneurysms (AAAs). The purpose of this study is to examine the effects of chymase inhibitor, NK3201, on the MMP-9 activity and development of AAA in the angiotensin II-induced apolipoprotein E (apoE)-deficient mice. Method: Angiotensin II (1000ng/kg/min) (vehicle group) or saline (control group) were infused into 16-week-old male apoE-deficient mice for 4 weeks. To examine the effect of chymase inhibition for AAA, we administered NK3201 (30mg/kg/day) to angiotensin II-infused group (NK3201-treated group) for the same period. At the end of angiotensin II infusion, we measured the diameters of suprarenal and infrarenal aorta. AAA severities were scored using the suprarenal aortic diameter/infrarenal aortic diameter ratio and presence of thrombus formation, i.e. under 2.0 was 0, from 2.0 to 2.5 was 1, from 2.5 to 3.0 was 2, over 3.0 was 3, and presence of thrombus was 4. We also determined the chymase and MMP-9 activities using total aorta. Results: The scores that reflected the progression and severity of AAA were increased in vehicle group compared with control group ( 2.35±0.30 vs. 0.27±0.12, p<0.01). This progression was inhibited in NK3201-treated group compared with vehicle group (1.13±0.35, p<0.05 vs. vehicle group). Chymase activity was significantly increased in vehicle group compared with control group. MMP-9 activity was also increased in vehicle group, however it was decreased significantly in NK3201-treated group.Discussion: We demonstrated that chymase inhibition could reduce AAA progression through inhibition of MMP-9 in angiotensin II-induced apoE-deficient mice. Chymase inhibitor might be a novel strategy for preventing AAAs.

Wall Stresses Before and After Endovascular Repair of Abdominal Aortic Aneurysms

2004 ◽  
Author(s):  
Elena S. Di Martino ◽  
Ajay Bohra ◽  
Christine Scotti ◽  
Ender Finol ◽  
David A. Vorp
Keyword(s):  
Endovascular Aneurysm Repair ◽  
Three Dimensional ◽  
Invasive Procedure ◽  
Aortic Aneurysms ◽  
Aortic Tissue ◽  
Type I ◽  
Abdominal Aortic ◽  
Before And After ◽  
Anchoring System ◽  
Three Dimensional Finite Element

Endovascular aneurysm repair (EVAR) technique is a minimally invasive procedure approach to abdominal aortic aneurysm (AAA) repair. Following EVAR, isolated aortic tissue starts remodeling after the new blood path is established. The commercially available endovascular grafts (EVG) have been found to be prone to Type I endoleak, which is re-pressurization of the degenerated AAA sac following a breach in the seal mechanism of the EVG or migration due to failure of the mechanism holding the graft in place (Chuter, 2002) These inadequacies of EVGs might be attributed to the effect of non-optimal design of graft anchoring system. In the present study, we utilized pre-operative and post-operative computer tomography (CT) data with previously derived material properties to construct three-dimensional finite element (FE) models for AAA before and after the EVAR procedure. We studied the nature of stresses acting on the aorta before and after EVAR. In particular we investigated the physical forces acting on the EVG and how they are transferred to the aortic wall at graft anchoring sites.

Endoluminal AAA Repair Using Intravascular Ultrasound for Graft Planning and Deployment: A 2-Year Community-Based Experience

2003 ◽  
Vol 10 (3) ◽  
pp. 463-475 ◽  
Author(s):  
David P. Slovut ◽  
Lewis C. Ofstein ◽  
J. Michael Bacharach
Keyword(s):  
Intravascular Ultrasound ◽  
Stent Graft ◽  
Atherosclerotic Plaque ◽  
Aortic Aneurysms ◽  
Graft Occlusion ◽  
High Grade ◽  
Aortic Neck ◽  
Abdominal Aortic ◽  
Increased Risk ◽  
Stent Graft Repair

Purpose: To examine the effectiveness of intravascular ultrasound (IVUS) and digital subtraction angiography (DSA) for preoperative planning and intraoperative deployment of stent-grafts to treat abdominal aortic aneurysms. Methods: One hundred seventy patients (143 men; mean age 73.6±7.2 years, range 51–89) underwent successful DSA and IVUS to determine suitability for stent-graft repair. Patients subsequently received the AneuRx (n=157) or Ancure (n=13) device; intraprocedural IVUS was used to survey the proximal endograft for proper apposition to the aortic wall. Results: Reliable preoperative IVUS measurements were obtained in all patients. Plaque morphology was assessed in 140 (82.3%) aortic necks; in 36 (25.7%), preoperative IVUS showed high-grade atherosclerotic plaque in the nonaneurysmal abdominal aortic neck. The procedure was successful in 168 (98.8%) cases (1 [0.6%] acute conversion and 1 access failure). There were 2 (1.2%) periprocedural deaths related to bowel ischemia. Four (2.3%) patients developed graft occlusion/kinking and 2 (1.2%) developed renal failure requiring dialysis within 30 days. Multivariate logistic regression analysis revealed that female gender (p=0.0247), a short nonaneurysmal aortic neck (p=0.0185), and presence of high-grade atherosclerotic plaque (p=0.0185) correlated with major acute complications. Over a mean 10.4-month follow-up (range 1–25), 11 patients died of unrelated causes; there was no known AAA rupture or device failure. The Kaplan-Meier estimate of survival at 1 year was 91.0%±2.8%. Sixteen (9.4%) patients underwent 17 secondary procedures for endoleak or graft limb occlusion at a mean 5.4 months after stent-graft repair (freedom from secondary intervention at 1 year 86.5%±3.2%). Conclusions: Our findings suggest that IVUS may identify patients at increased risk of major adverse complications following endovascular repair. The combination of IVUS and DSA for endoluminal stent-graft planning and placement provides excellent short- and mid-term patient outcomes.

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