Abstract 105: Increased Dynamic Mechanical Energy Dissipation in Human Abdominal Aortic Aneurysm

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Doran S Mix ◽  
Ibrahima Bah ◽  
Sandra A Toth ◽  
Michael C Stoner ◽  
Adam J Doyle ◽  
...  
Keyword(s):  
Energy Dissipation ◽  
Energy Loss ◽  
Mechanical Testing ◽  
Mechanical Energy ◽  
Aortic Aneurysms ◽  
Aortic Tissue ◽  
Loss Ratio ◽  
Tissue Viability ◽  
Static Modulus ◽  
Abdominal Aortic

Objectives: Individualized patient rupture risk for abdominal aortic aneurysms (AAA) remains elusive due to a limited understanding of the biomechanical events that trigger aneurysm growth and aortic wall failure. To date there has been a paucity of data describing how physiologic pulsatile energy is stored (E') and lost (E'') from AAA tissue. Our hypothesis is that AAA tissue dissipates more cyclic energy at a physiologic frequency, as determined by (E''/ E'), when compared to healthy aortic tissue. Methods: Human healthy aortic and AAA samples were obtained from cadaveric and surgical specimens. Specimens were stored at 4 o C in 0.9%NS and mechanically tested within 36 hrs of explant. Uniaxial mechanical testing (ADMET BioTense) was performed in the circumferential orientation with the tissue pre-loaded to an equivalent physiologic stress of a 5 cm at a 110 mmHg mean pressure. A sinusoidal ±5% strain was applied at 1 Hz for 40 cycles with simultaneous force measurements. After mechanical testing, immunohistochemical staining was performed to confirm tissue viability. Results: AAA tissue was significantly stiffer when compared to healthy aorta, as demonstrated by a greater average static modulus (E) 1555.4 ± 384 vs. 970 ± 128 kPa (n=5, p=0.03). Dynamic testing of the AAA tissue noted a significantly greater energy loss (E'') 137.8±36.7 vs. 43.1±21.7 (p<0.01) and loss ratio (E''/ E') 0.090 ± 0.023 vs. 0.044 ± 0.023 (p=0.02), when compared to normal specimens. Figure #1 compares the static modulus (E) to the loss ratio (E''/ E') for the aortic tissue specimens. Histologic analysis confirmed tissue viability during of all specimens. Conclusions: Our data demonstrates that AAA tissue dissipates more energy (E'') and has a greater energy loss ratio (E''/ E'), suggesting that more pulsatile energy is dissipated in diseased tissue. Future work is needed to determine how this energy dissipation influences the biologic pathogenesis of AAA growth and rupture.

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.

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.

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.

Abstract 109: Tumor Necrosis Factor Inducible Gene 6 Protein (TSG-6) is Highly Expressed in Human Abdominal Aortic Aneurysms

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
S. Keisin Wang ◽  
Linden Green ◽  
Jie Xie ◽  
Raghu Motaganahalli ◽  
Andres Fajardo ◽  
...  
Keyword(s):  
Risk Factor ◽  
Aortic Wall ◽  
Mononuclear Cells ◽  
Tissue Concentration ◽  
Macrophage Polarization ◽  
Aortic Aneurysms ◽  
Aortic Tissue ◽  
Abdominal Aortic ◽  
Anti Inflammatory

Objective: The formation of an abdominal aortic aneurysm (AAA) is characterized by a dominance of pro-inflammatory forces that result in smooth muscle cell apoptosis, extra-cellular matrix degradation, and progressive diameter expansion. Additional defects in the anti-inflammatory response may also contribute to AAA progression, however have yet to be characterized robustly. Here, we describe the role of the anti-inflammatory cytokine TSG-6 (TNF-stimulated gene-6) in AAA formation. Methods: Blood and aortic tissue samples were collected from patients undergoing elective AAA screening and open surgical AAA repair. Aortic specimens collected were preserved for IHC or immediately assayed after tissue homogenization. Cytokine concentrations in tissue and plasma were assayed by ELISA. All immune cell populations were assayed using FACS analysis. In vitro, macrophage polarization from monocytes were performed with young, healthy donor PBMCs. Results: TSG-6 was found to be abnormally elevated in both the plasma and aorta of patients with AAA compared to healthy and risk-factor matched non-AAA donors. We observed the highest tissue concentration of TSG-6 in the less diseased proximal and distal shoulders compared to the central aspect of the aneurysm. IHC localized the majority of TSG-6 to the tunica media with minor expression in the tunica adventitia of the aortic wall. Higher concentrations of both M1 and M2 macrophages where also observed in the aortic wall, however M1/M2 ratios were unchanged from healthy controls. Additionally, we observed no difference in M1/M2 ratios in the peripheral blood of risk-factor matched non-AAA and AAA patients. Interesting, TSG-6 inhibited the polarization of the anti-inflammatory M2 phenotype in vitro . Conclusions: AAA formation results from an imbalance of inflammatory forces causing aortic wall infiltration of mononuclear cells leading to resultant vessel breakdown. From our results, we suggest TSG-6 is elevated in the AAA patient as a compensatory anti-inflammatory feedback mechanism. However, it’s effects may be abrogated by defects in CD44, its cognate receptor or downstream signaling pathways, future areas for investigation.

Anisotropic Wall Mechanics of Abdominal Aortic Aneurysms

2008 ◽  
Author(s):  
Giampaolo Martufi ◽  
Jose F. Rodriguez ◽  
Ender A. Finol
Keyword(s):  
Three Dimensional ◽  
Wall Stress ◽  
Aortic Aneurysms ◽  
Constitutive Law ◽  
Intraluminal Pressure ◽  
Aortic Tissue ◽  
Unruptured Aneurysms ◽  
Abdominal Aortic ◽  
Dimensional Reconstruction ◽  
Tissue Specimens

The prevalence of AAA is growing along with population age and according to different studies AAA rupture is the 13th most common cause of death in the U.S., causing an estimated 15,000 deaths per year. In biomechanical terms, AAA rupture is a phenomenon that occurs when the developing mechanical stresses within the aneurysm inner wall, as a result of the exerted intraluminal pressure, exceed the failure strength of the aortic tissue. To obtain a reliable estimation of wall stress, it is necessary to perform an accurate three-dimensional reconstruction of the AAA geometry and model an appropriate constitutive law for the aneurysmal tissue material characterization. In this regard, a recent study on the biaxial mechanical behavior of human AAA tissue specimens [1] demonstrates that aneurysmal arterial tissue behaves mechanically anisotropic. The objectives of the present work are to determine the effect of material anisotropy of the aneurysmal abdominal aorta on wall stress distribution and to establish a comparison of wall mechanics between ruptured and unruptured aneurysms.

scholarly journals Comparative Study of Aortic Wall Stress According to Geometric Parameters in Abdominal Aortic Aneurysms

2021 ◽  
Vol 11 (7) ◽  
pp. 3195
Author(s):  
Ji-Hun You ◽  
Chung Won Lee ◽  
Up Huh ◽  
Chi-Seung Lee ◽  
Dongman Ryu
Keyword(s):  
Aortic Rupture ◽  
Wall Stress ◽  
Aortic Aneurysms ◽  
Aortic Tissue ◽  
Factors Affecting ◽  
Abdominal Aortic ◽  
Geometric Factors ◽  
Measurement Results ◽  
Simulation Scenario ◽  
Peak Wall Stress

In abdominal aortic aneurysm (AAA), the rupture of the aortic tissue is directly related to wall stress. Thus, the investigation of maximum wall stress is a necessary procedure to predict the aortic rupture in AAA. In this study, computational simulations were performed to investigate the correlation between peak wall stress (PWS) and AAA geometry. The Holzapfel model and various orientations of the collagen fibers and thicknesses of the layers of the aorta were employed in the simulation. The material constants used in the Holzapfel model were estimated from the examination and analysis of the biaxial tensile test results of the normal abdominal aorta and AAA. The aneurysm diameter, height, neck angle, and iliac angle were selected as geometric factors affecting the AAA rupture. In addition, a simulation scenario was conceived and created based on the measurement results using the computed tomography data of patients with AAA. Accordingly, the correlation between the PWS and AAA geometry was estimated.

scholarly journals Multiplex immunohistochemistry differences between Q fever and atherosclerotic abdominal aortic aneurysms indicate immune suppression

2021 ◽  
Author(s):  
Kimberley R.G. Cortenbach ◽  
Alexander H.J. Staal ◽  
Teske Schoffelen ◽  
Mark A.J. Gorris ◽  
Lieke L. Van der Woude ◽  
...  
Keyword(s):  
T Cells ◽  
Q Fever ◽  
Cytotoxic T Cells ◽  
Adaptive Immune System ◽  
Research Area ◽  
Aortic Aneurysms ◽  
Aortic Tissue ◽  
Local Inflammation ◽  
Effector Cells ◽  
Abdominal Aortic

Background: Chronic Q fever is a zoonosis caused by the bacterium Coxiella burnetii which can manifest as infection of an abdominal aortic aneurysm (AAA). Antibiotic therapy often fails, resulting in severe morbidity and high mortality. Whereas previous studies have focused on inflammatory processes in blood, the aim of this study was to investigate local inflammation in aortic tissue. Methods: Multiplex immunohistochemistry was used to investigate local inflammation in Q fever AAAs compared to atherosclerotic AAAs in aorta tissue specimen. Two six-plex panels were used to study both the innate and adaptive immune system. Results: Q fever AAAs and atherosclerotic AAAs contained similar numbers of CD68+ macrophages and CD3+ T cells. However, in Q fever AAAs the number of CD68+CD206+ M2 macrophages was increased, while expression of GM-CSF was decreased compared to atherosclerotic AAAs. Furthermore, Q fever AAAs showed an increase in both the number of CD8+ cytotoxic T cells and CD3+FoxP3+ regulatory T cells. Lastly, Q fever AAAs did not contain any well-defined granulomas. Conclusions: These findings demonstrate that despite the presence of pro-inflammatory effector cells, there is an immune suppressive micro environment in Q fever AAA resulting in persistent local infection with C. burnetii. Funding: This work was supported by SCAN consortium: European Research Area - CardioVascualar Diseases (ERA-CVD) grant [JTC2017-044] and TTW-NWO open technology grant [STW-14716].

Abstract 253: Abdominal Aortic Aneurysms: Protein Targets for Autoimmunity

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Abhijit Ghosh ◽  
Angela Pechota ◽  
John S Futchko ◽  
Omar Sadiq ◽  
Peter K Henke ◽  
...  
Keyword(s):  
Smoking Status ◽  
Negative Control ◽  
Aortic Aneurysms ◽  
Aortic Tissue ◽  
Western Blots ◽  
Molecular Weights ◽  
Ms Analysis ◽  
Abdominal Aortic ◽  
Parent Protein ◽  
Sequence Homologies

Objectives: The vast majority of Abdominal Aortic Aneurysm (AAA) patients have a history of smoking. The current hypothesis is that smoking induces post-translational protein modifications within the abdominal aorta resulting in site-specific antigenic targets for humoral immunity, and leads to a complex inflammatory milieu that ultimately gives rise to mature AAAs. Methods: Plasma samples from patients with AAAs were separated by smoking status (Non-smoker = NS [n = 5]; Smoker = S [n = 15]; Prior Smoker = PS [n = 36]). Aortic wall was harvested from AAA (n = 5) and healthy control aorta (n = 5). Membrane proteins were extracted from AAA aortas by phase separation and bound to affinity columns. Plasma from NS, S, and PS groups was passed through these columns to isolate immunoglobulins (eluted IgGs). Duplicate samples of pooled control aortic tissue proteins underwent electrophoresis for Western blotting and Coomassie staining. Western blots were developed with eluted IgGs from the NS, S, and PS groups as well as IgGs from healthy volunteers as negative control. The Western blots were analyzed for differences in banding patterns between NS and S or PS groups and the corresponding proteins from Coomassie stained gels were excised for Mass Spectrometry (LC-MS/MS analysis). Results: Western blot experiments revealed a ∼38 kD band in NS but no correlating band in S and PS groups, as well as ∼22 kD and ∼33 kD bands present in S and PS but no correlating bands in the NS group. LC-MS/MS analysis of these 3 bands identified the encompassed proteins as having sequence homologies with TROPOMYOSIN 1, TROPOMYOSIN 2, TRANSGELIN, INTEGRIN BETA-1, VERSICAN, PEROXIREDOXIN 2 and OSTEOGLYCIN (Mimecan), and that these proteins differed in relative abundance between the three groups. Conclusions: We identified putative proteins in normal human aortas that could represent autoimmune targets leading to AAA development. The discrepancy between the molecular weights of putative targets and the bands used for LC-MS/MS analysis possibly reflects post-translational processing of the larger parent protein resulting in auto-antigenicity.

Abstract 418: Microfibrillar-Associated Protein 4 Deficiency Reduces Size and Incidence Rate of Angiotensin II Induced Abdominal Aortic Aneurysms in Mice

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Katrine L Kirketerp-Møller ◽  
Jane Stubbe ◽  
Anders Schlosser ◽  
Karin Kejling ◽  
Jesper B Møller ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Incidence Rate ◽  
Aortic Aneurysms ◽  
Aortic Tissue ◽  
Aortic Blood Flow ◽  
Infrarenal Aorta ◽  
Arterial Blood ◽  
Elastin Degradation ◽  
Abdominal Aortic

Microfibrillar-associated protein 4 (MFAP4) is an extracellular matrix (ECM) protein primarily located in elastic arteries. It can bind elastin and collagen, and furthermore activate vascular cells through cellular integrin binding and modulate matrix metalloprotinase (MMP) activity. We hypothesized that lack of MFAP4 would decrease vascular inflammation and abdominal aortic aneurysm (AAA) formation. AAA was induced in 9-11 week old mice using two experimental mouse models: 1) Male Mfap4 -/- /ApoE -/- double knock-out (dKO) and ApoE -/- littermate control mice were feed western diet and subjected to continuously angiotensin II (AngII, 1000 ng/kg/min) infusion for 9-28 days via subcutaneous osmotic mini-pumps. Arterial blood pressure was measured in the femoral artery. 2) 1.5 U/mL elastase was infused into the infrarenal aorta in Mfap4 -/- and littermate Mfap4 +/+ mice for 5 minutes. Aortic blood flow was restored and the mice recovered for 9-16 days. Aortic diameter was measured in mice subjected to AngII or elastase infusion at day 28 and 16 respectively. MMP activity was detected by zymography. No difference in AAA formation was observed between genotypes after elastase perfusion. In response to AngII infusion dKO mice showed a significantly decrease in AAA diameter and incidence rate compared to ApoE -/- mice. AngII-induced increase in blood pressure was not dependent of MFAP4. However, there was decreased aortic arch atherosclerotic plaque formation, MMP2 and MMP9 activity in aortic tissue from dKO mice compared to ApoE -/- mice. Furthermore there was a non-significant tendency of decreased elastin degradation score in the AngII infused dKO mice, however this was not observed in the elastase perfused mice. Activity of MMP12 and extent of infiltrating leukocytes in aneurysmal tissue from both models will be further investigated. In conclusion we observed a decreased AAA formation and MMP activity in Mfap4 -/- /ApoE -/- mice which was not explained by variation in blood pressure or altered elastin degradation. The data suggest that MFAP4 induces MMP2-activity and thus the propensity for AAA formation.

Neutrophil Elastase-Derived Fibrin Degradation Products Indicate Presence of Abdominal Aortic Aneurysms and Correlate with Intraluminal Thrombus Volume

2018 ◽  
Vol 118 (02) ◽  
pp. 329-339 ◽  
Author(s):  
Moritz Lindquist Liljeqvist ◽  
Angela Silveira ◽  
Rebecka Hultgren ◽  
Siw Frebelius ◽  
Mariette Lengquist ◽  
...  
Keyword(s):  
Mechanical Stress ◽  
Neutrophil Elastase ◽  
Degradation Products ◽  
Abdominal Aortic Aneurysms ◽  
Aortic Aneurysms ◽  
Aortic Tissue ◽  
Fibrin Degradation Products ◽  
Abdominal Aortic ◽  
Separate Cohort ◽  
D Dimer

Background The intraluminal thrombi (ILT) of abdominal aortic aneurysms (AAA) contain neutrophils, which can secrete elastase. We evaluated whether plasma neutrophil elastase-derived cross-linked fibrin degradation products (E-XDP) could reveal the presence, size and mechanical stress of AAAs and its ILTs. Methods E-XDP and D-dimer were measured in plasma from 37 male patients with AAA and 42 male controls. The ILT volumes of the AAAs and any coexisting aneurysms could be measured in 29 patients and finite element analysis was performed to estimate mechanical stress of the ILT. E-XDP, neutrophil elastase and neutrophil marker CD66acd were evaluated in aortic tissue with immunohistochemistry (IHC). The association between ILT volume and E-XDP was validated in a separate cohort (n = 51). Results E-XDP levels were elevated in patients with AAA compared with controls (p = 5.8e-13), indicated AAA with 98% sensitivity, 86% specificity and increased with presence of coexisting aneurysms. The association between AAA and increased E-XDP was independent of smoking, comorbidities and medication. E-XDP correlated with volume of all ILTs (r = 0.76, p = 4.5e-06), mean ILT stress (r = 0.46, p = 0.013) and the volume of the AAA-associated ILT (r = 0.64, p = 0.00017). E-XDP correlated stronger with ILT volume compared with D-dimer (r = 0.76 vs. r = 0.64, p = 0.018). The correlation between E-XDP and ILT volume was validated in the separate cohort (r = 0.53, p = 7.6e-05). IHC revealed E-XDP expression in the ILT, spatially related to neutrophil elastase and neutrophils. Conclusion E-XDP is a marker of the presence of AAA and coexisting aneurysms as well as the volume and mechanical stress of the ILT.

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