scholarly journals Morphological and Biomechanical Differences in the Elastase and AngIIapoE−/−Rodent Models of Abdominal Aortic Aneurysms

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Evan H. Phillips ◽  
Alexa A. Yrineo ◽  
Hilary D. Schroeder ◽  
Katherine E. Wilson ◽  
Ji-Xin Cheng ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Aortic Aneurysms ◽  
Circulating Biomarkers ◽  
Induction Method ◽  
Future Studies ◽  
Disease Characteristics ◽  
Abdominal Aortic ◽  
Extracellular Matrix Molecules ◽  
Biomechanical Parameters

An abdominal aortic aneurysm (AAA) is a potentially fatal cardiovascular disease with multifactorial development and progression. Two preclinical models of the disease (elastase perfusion and angiotensin II infusion in apolipoprotein-E-deficient animals) have been developed to study the disease during its initiation and progression. To date, most studies have usedex vivomethods to examine disease characteristics such as expanded aortic diameter or analytic methods to look at circulating biomarkers. Herein, we provide evidence fromin vivoultrasound studies of the temporal changes occurring in biomechanical parameters and macromolecules of the aortic wall in each model. We present findings from 28-day studies in elastase-perfused rats and AngIIapoE−/−mice. While each model develops AAAs specific to their induction method, they both share characteristics with human aneurysms, such as marked changes in vessel strain and blood flow velocity. Histology and nonlinear microscopy confirmed that both elastin and collagen, both important extracellular matrix molecules, are similarly affected in their levels and spatial distribution. Future studies could make use of the differences between these models in order to investigate mechanisms of disease progression or evaluate potential AAA treatments.

scholarly journals Effect of Doxycycline on Survival in Abdominal Aortic Aneurysms in a Mouse Model

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Lisa C. Adams ◽  
Julia Brangsch ◽  
Jan O. Kaufmann ◽  
Dilyana B. Mangarova ◽  
Jana Moeckel ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Ex Vivo ◽  
Endothelial Damage ◽  
Aortic Aneurysms ◽  
Clinical Dose ◽  
Doxycycline Treatment ◽  
Abdominal Aortic ◽  
Significant Difference ◽  
Aneurysm Growth

Background. Currently, there is no reliable nonsurgical treatment for abdominal aortic aneurysm (AAA). This study, therefore, investigates if doxycycline reduces AAA growth and the number of rupture-related deaths in a murine ApoE−/− model of AAA and whether gadofosveset trisodium-based MRI differs between animals with and without doxycycline treatment. Methods. Nine ApoE−/− mice were implanted with osmotic minipumps continuously releasing angiotensin II and treated with doxycycline (30 mg/kg/d) in parallel. After four weeks, MRI was performed at 3T with a clinical dose of the albumin-binding probe gadofosveset (0.03 mmol/kg). Results were compared with previously published wild-type control animals and with previously studied ApoE−/− animals without doxycycline treatment. Differences in mortality were also investigated between these groups. Results. In a previous study, we found that approximately 25% of angiotensin II-infused ApoE−/− mice died, whereas in the present study, only one out of 9 angiotensin II-infused and doxycycline-treated ApoE−/− mice (11.1%) died within 4 weeks. Furthermore, doxycycline-treated ApoE−/− mice showed significantly lower contrast-to-noise (CNR) values ( p = 0.017 ) in MRI compared to ApoE−/− mice without doxycycline treatment. In vivo measurements of relative signal enhancement (CNR) correlated significantly with ex vivo measurements of albumin staining (R2 = 0.58). In addition, a strong visual colocalization of albumin-positive areas in the fluorescence albumin staining with gadolinium distribution in LA-ICP-MS was shown. However, no significant difference in aneurysm size was observed after doxycycline treatment. Conclusion. The present experimental in vivo study suggests that doxycycline treatment may reduce rupture-related deaths in AAA by slowing endothelial damage without reversing aneurysm growth.

scholarly journals [18F]Fluorothymidine Uptake in the Porcine Pancreatic Elastase-Induced Model of Abdominal Aortic Aneurysm

2021 ◽  
Vol 7 (8) ◽  
pp. 130
Author(s):  
Richa Gandhi ◽  
Joanna Koch-Paszkowski ◽  
Charalampos Tsoumpas ◽  
Marc A. Bailey
Keyword(s):  
Murine Model ◽  
Ex Vivo ◽  
Aortic Rupture ◽  
Aortic Aneurysms ◽  
Preclinical Model ◽  
Pancreatic Elastase ◽  
Abdominal Aortic ◽  
Pet Ct ◽  
Porcine Pancreatic Elastase

The porcine pancreatic elastase (PPE) model is a common preclinical model of abdominal aortic aneurysms (AAA). Some notable characteristics of this model include the low aortic rupture rate, non-progressive disease course, and infra-renal AAA formation. Enhanced [18F]fluorothymidine ([18F]FLT) uptake on positron emission tomography/computed tomography (PET/CT) has previously been reported in the angiotensin II-induced murine model of AAA. Here, we report our preliminary findings of investigating [18F]FLT uptake in the PPE murine model of AAA. [18F]FLT uptake was found to be substantially increased in the abdominal areas recovering from the surgery, whilst it was not found to be significantly increased within the PPE-induced AAA, as confirmed using in vivo PET/CT and ex vivo whole-organ gamma counting (PPE, n = 7; controls, n = 3). This finding suggests that the [18F]FLT may not be an appropriate radiotracer for this specific AAA model, and further studies with larger sample sizes are warranted to elucidate the pathobiology contributing to the reduced uptake of [18F]FLT in this model.

scholarly journals Animal Model Dependent Response to Pentagalloyl Glucose in Murine Abdominal Aortic Injury

2021 ◽  
Vol 10 (2) ◽  
pp. 219
Author(s):  
Jennifer L. Anderson ◽  
Elizabeth E. Niedert ◽  
Sourav S. Patnaik ◽  
Renxiang Tang ◽  
Riley L. Holloway ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Aortic Injury ◽  
Aortic Aneurysms ◽  
Maximum Diameter ◽  
Ultrasound Images ◽  
Infrarenal Aorta ◽  
High Frequency Ultrasound ◽  
Abdominal Aortic ◽  
Pentagalloyl Glucose

Abdominal aortic aneurysms (AAAs) are a local dilation of the aorta and are associated with significant mortality due to rupture and treatment complications. There is a need for less invasive treatments to prevent aneurysm growth and rupture. In this study, we used two experimental murine models to evaluate the potential of pentagalloyl glucose (PGG), which is a polyphenolic tannin that binds to and crosslinks elastin and collagen, to preserve aortic compliance. Animals underwent surgical aortic injury and received 0.3% PGG or saline treatment on the adventitial surface of the infrarenal aorta. Seventeen mice underwent topical elastase injury, and 14 mice underwent topical calcium chloride injury. We collected high-frequency ultrasound images before surgery and at 3–4 timepoints after. There was no difference in the in vivo effective maximum diameter due to PGG treatment for either model. However, the CaCl2 model had significantly higher Green–Lagrange circumferential cyclic strain in PGG-treated animals (p < 0.05). While ex vivo pressure-inflation testing showed no difference between groups in either model, histology revealed reduced calcium deposits in the PGG treatment group with the CaCl2 model. These findings highlight the continued need for improved understanding of PGG’s effects on the extracellular matrix and suggest that PGG may reduce arterial calcium accumulation.

Investigation of the Observed Rupture Lines in Abdominal Aortic Aneurysms Using Crack Propagation Simulations

2019 ◽  
Vol 141 (7) ◽  
Author(s):  
S. Attarian ◽  
S. Xiao ◽  
T. C. Chung ◽  
E. S. da Silva ◽  
M. L. Raghavan
Keyword(s):  
Crack Propagation ◽  
Ex Vivo ◽  
Wall Stress ◽  
Abdominal Aortic Aneurysms ◽  
Aortic Aneurysms ◽  
Abdominal Aortic ◽  
Subject Specific ◽  
Study Population ◽  
Peak Wall Stress

The objective of the study is to use crack propagation simulation to study the rupture site characteristics in ruptured abdominal aortic aneurysms (AAA). In a study population of four ruptured AAA harvested whole from cadavers, the rupture lines were precisely documented. The wall properties such as thickness and material parameters were experimentally determined. Using subject-specific three-dimensional (3D) geometry and a finite elastic isotropic material model with subject-specific parameters, crack propagation simulations were conducted based on basic fracture mechanics principles to investigate if and how localized weak spots may have led to the rupture lines observed upon harvest of ruptured AAA. When an initial crack was imposed at the site of peak wall stress, the propagated path did not match the observed rupture line. This indicates that in this study population, the peak wall stress was unlikely to have caused the observed rupture. When cracks were initiated at random locations in the AAA along random orientations and for random initial lengths, the orientation of the resulting propagated rupture line was always longitudinal. This suggests that the AAA morphology predisposes the AAA to rupture longitudinally, which is consistent with observations. And finally, it was found that, in this study population, rupture may have initiated at short segments of less than 1 cm length that then propagated to the observed rupture lines. This finding provides some guidance for the spatial resolution (approx. 1 cm) of weak spots to investigate for in AAA during ex vivo experimental and in vivo elastography studies. The small study population and lack of a reliable failure model for AAA tissue make these findings preliminary.

scholarly journals Targeting the Extracellular Matrix in Abdominal Aortic Aneurysms Using Molecular Imaging Insights

2021 ◽  
Vol 22 (5) ◽  
pp. 2685
Author(s):  
Lisa Adams ◽  
Julia Brangsch ◽  
Bernd Hamm ◽  
Marcus R. Makowski ◽  
Sarah Keller
Keyword(s):  
Extracellular Matrix ◽  
Molecular Imaging ◽  
Molecular Targets ◽  
Abdominal Aortic Aneurysms ◽  
Aortic Aneurysms ◽  
Type I ◽  
Target Tissue ◽  
Pharmacologic Treatment ◽  
Abdominal Aortic

This review outlines recent preclinical and clinical advances in molecular imaging of abdominal aortic aneurysms (AAA) with a focus on molecular magnetic resonance imaging (MRI) of the extracellular matrix (ECM). In addition, developments in pharmacologic treatment of AAA targeting the ECM will be discussed and results from animal studies will be contrasted with clinical trials. Abdominal aortic aneurysm (AAA) is an often fatal disease without non-invasive pharmacologic treatment options. The ECM, with collagen type I and elastin as major components, is the key structural component of the aortic wall and is recognized as a target tissue for both initiation and the progression of AAA. Molecular imaging allows in vivo measurement and characterization of biological processes at the cellular and molecular level and sets forth to visualize molecular abnormalities at an early stage of disease, facilitating novel diagnostic and therapeutic pathways. By providing surrogate criteria for the in vivo evaluation of the effects of pharmacological therapies, molecular imaging techniques targeting the ECM can facilitate pharmacological drug development. In addition, molecular targets can also be used in theranostic approaches that have the potential for timely diagnosis and concurrent medical therapy. Recent successes in preclinical studies suggest future opportunities for clinical translation. However, further clinical studies are needed to validate the most promising molecular targets for human application.

Abdominal Aortic Aneurysm: From Clinical Imaging to Realistic Replicas

2013 ◽  
Vol 136 (1) ◽  
Author(s):  
Sergio Ruiz de Galarreta ◽  
Aitor Cazón ◽  
Raúl Antón ◽  
Ender A. Finol
Keyword(s):  
Wall Thickness ◽  
Physiological Stress ◽  
Ex Vivo ◽  
Casting Process ◽  
Aortic Aneurysms ◽  
Optical Methods ◽  
Patient Specific ◽  
Uniaxial Tensile ◽  
Element Analysis ◽  
Abdominal Aortic

The goal of this work is to develop a framework for manufacturing nonuniform wall thickness replicas of abdominal aortic aneurysms (AAAs). The methodology was based on the use of computed tomography (CT) images for virtual modeling, additive manufacturing for the initial physical replica, and a vacuum casting process and range of polyurethane resins for the final rubberlike phantom. The average wall thickness of the resulting AAA phantom was compared with the average thickness of the corresponding patient-specific virtual model, obtaining an average dimensional mismatch of 180 μm (11.14%). The material characterization of the artery was determined from uniaxial tensile tests as various combinations of polyurethane resins were chosen due to their similarity with ex vivo AAA mechanical behavior in the physiological stress configuration. The proposed methodology yields AAA phantoms with nonuniform wall thickness using a fast and low-cost process. These replicas may be used in benchtop experiments to validate deformations obtained with numerical simulations using finite element analysis, or to validate optical methods developed to image ex vivo arterial deformations during pressure-inflation testing.

Abstract 107: Depletion of Plasmacytoid Dendritic Cells Inhibits Experimental Abdominal Aortic Aneurysms

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Baohui Xu ◽  
Haojun Xuan ◽  
Naoki Fujimura ◽  
Sara A Michie ◽  
Ronald L Dalman
Keyword(s):  
Dendritic Cells ◽  
Inflammatory Diseases ◽  
Myeloid Cells ◽  
Abdominal Aortic Aneurysms ◽  
Plasmacytoid Dendritic Cells ◽  
Aortic Aneurysms ◽  
Major Type ◽  
Abdominal Aortic

Introduction: Abdominal aortic aneurysms (AAA) manifest histologic features consistent with other chronic inflammatory diseases. Infiltrating mural myeloid cells (e.g. macrophages) are already recognized as important contributors to aneurysm pathogenesis, however, the role of plasmacytoid dendritic cells (pDC), major type 1 interferon-producing myeloid cells involving in autoimmune diseases and atherosclerosis, has not been previously investigated in this context. Methods and Results: AAAs were created in 12 week old male C57BL/6J mice by transient intra-aortic infusion of porcine pancreatic elastase (PPE). AAA development and progression were assessed via serial ultrasound determination of aortic diameter in vivo , and histology at sacrifice. The fraction of circulating leukocytes identified as pDCs was significantly increased immediately following PPE infusion (aneurysm initiation). Treatment with mPDCA-1 mAb (400 μg i.p. q.o.d.), beginning one day prior to PPE infusion, depleted more than 90% of bone marrow, spleen and peripheral blood pDCs (data not shown) and suppressed subsequent aneurysm development and progression compared to that noted in PPE-infused mice treated with control mAb. mPDCA-1 treatment promoted aortic medial elastin and smooth muscle preservation, while limiting mural macrophage accumulation and neocapillary formation. Conclusion: These findings suggest a role for plasmacytoid dendritic cells in promoting the initiation and progression of experimental abdominal aortic aneurysms.

Method for Incorporating Three-Dimensional Residual Stresses Into Patient-Specific Simulations of Arteries

2013 ◽  
Author(s):  
David M. Pierce ◽  
Thomas E. Fastl ◽  
Hannah Weisbecker ◽  
Gerhard A. Holzapfel ◽  
Borja Rodriguez-Vila ◽  
...  
Keyword(s):  
Medical Imaging ◽  
Three Dimensional ◽  
Constitutive Models ◽  
Abdominal Aortic Aneurysms ◽  
Aortic Aneurysms ◽  
Patient Specific ◽  
Abdominal Aortic ◽  
Model Geometry ◽  
Reconstructed Model

Through progress in medical imaging, image analysis and finite element (FE) meshing tools it is now possible to extract patient-specific geometries from medical images of, e.g., abdominal aortic aneurysms (AAAs), and thus to study clinically relevant problems via FE simulations. Medical imaging is most often performed in vivo, and hence the reconstructed model geometry in the problem of interest will represent the in vivo state, e.g., the AAA at physiological blood pressure. However, classical continuum mechanics and FE methods assume that constitutive models and the corresponding simulations start from an unloaded, stress-free reference condition.

A Review of the In Vivo and In Vitro Biomechanical Behavior and Performance of Postoperative Abdominal Aortic Aneurysms and Implanted Stent-Grafts

2008 ◽  
Vol 15 (4) ◽  
pp. 468-484 ◽  
Author(s):  
Timothy J. Corbett ◽  
Anthony Callanan ◽  
Liam G. Morris ◽  
Barry J. Doyle ◽  
Pierce A. Grace ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysms ◽  
Aortic Aneurysms ◽  
Stent Grafts ◽  
Biomechanical Behavior ◽  
Abdominal Aortic ◽  
And Performance
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