Abdominal Aortic Aneurysm Evolution Research Articles

HDL metabolism and functions impacting on cell cholesterol homeostasis are specifically altered in patients with abdominal aortic aneurysm.

BackgroundThe etiopathogenesis of abdominal aortic aneurysm (AAA) is still unclarified, but vascular inflammation and matrix metalloproteases activation have a recognized role in AAA development and progression. Circulating lipoproteins are involved in tissue inflammation and repair, particularly through the regulation of intracellular cholesterol, whose excess is associated to cell damage and proinflammatory activation. We analyzed lipoprotein metabolism and function in AAA and in control vasculopathic patients, to highlight possible non-atherosclerosis-related, specific abnormalities.MethodsWe measured fluorometrically serum esterified/total cholesterol ratio, as an index of lecithin-cholesterol acyltransferase (LCAT) activity, and cholesteryl ester transfer protein (CETP) activity in patients referred to vascular surgery either for AAA (n=30) or stenotic aortic/peripheral atherosclerosis (n=21) having similar burden of cardiovascular risk factors and disease. We measured high-density lipoprotein (HDL)-cholesterol efflux capacity (CEC), through the ATP-binding cassette G1 (ABCG1) and A1 (ABCA1) pathways and serum cell cholesterol loading capacity (CLC), by radioisotopic and fluorimetric methods, respectively.ResultsWe found higher LCAT (+23%; p < 0.0001) and CETP (+49%; p < 0.0001) activity in AAA sera. HDL ABCG1-CEC was lower (−16%; p < 0.001) and ABCA1-CEC was higher (+31.7%; p < 0.0001) in AAA. Stratification suggests that smoking may partly contribute to these modifications. CEC and CETP activity correlated with CLC only in AAA.ConclusionsWe demonstrated that compared to patients with stenotic atherosclerosis, patients with AAA had altered HDL metabolism and functions involved in their anti-inflammatory and tissue repair activity, particularly through the ABCG1-related intracellular signaling. Clarifying the relevance of this mechanism for AAA evolution might help in developing new diagnostic parameters and therapeutic targets for the early management of this condition.

Persisting Type 2 Endoleaks Following EVAR for AAA Are Associated With AAA Expansion

Purpose: To determine the evolution of abdominal aortic aneurysm (AAA) diameter in the presence of persisting type 2 endoleaks (pEL2) following endovascular abdominal aortic aneurysm repair (EVAR). Materials and Methods: This is a retrospective, single-center, case-control study. All patients with pEL2 (pEL2 group, persisting for > 12 months) between 2004 and 2018 were identified and compared with a 1:1 age- and gender-matched control with no endoleak (control group). Primary outcome measures were freedom from AAA expansion and freedom from AAA shrinkage over time. AAA diameter measurements were performed on computed tomography angiography (CTA). Secondary outcome measures were survival, AAA-related mortality, reinterventions for pEL2, incidence of secondary type 1 endoleaks (EL1), and infrarenal aortic branch vessel anatomy. Results: A total of 773 patients were treated with EVAR for AAA between 2004 and 2018. Of them, 286 patients demonstrated type 2 endoleaks (EL2) in postoperative CTA or intraoperative angiography (37%). Forty-five of 286 EL2 (15.7%) were pEL2 (pEL2 group). Freedom from AAA expansion in the pEL2 group was 100%, 96.7%, 85.2%, and 54.3% after 1, 2, 3, and 4 years, respectively, compared with 100% after 1, 2, 3, and 4 years in the control group (p<0.01). Freedom from AAA shrinkage in the pEL2 group after 1, 2, 3, and 4 years was 95.5%, 90.4%, 90.4%, and 79.1%, respectively, compared with 86.7%, 34.8%, 19.3%, and 19.3% in the control group (p<0.01). Overall survival at 1, 2, 3, and 4 years was 100%, 97.6%, 95.0% and 95.0% in the pEL2 group and 100% at 1, 2, 3, and 4 years in the control group (p=0.17). There were no AAA-related deaths in either group. Patients with pEL2 had a significantly increased number of infrarenal aortic branches (p<0.05, respectively). Eighteen patients (40.0%) in the pEL2 group underwent 34 reinterventions for pEL2, with a median follow-up (FU) of 925 days (0–4173). Clinical success was achieved in 9 patients (50.0%). Four patients (8.9%) with pEL2 developed secondary EL1 after a median FU of 1278 days (662–2121). Conclusion: pEL2 are associated with AAA expansion during midterm FU. Further studies are warranted to evaluate the association of AAA expansion due to pEL2 with clinical outcomes to allow recommendations with regard to treatment indications.

Mechanical role of intraluminal thrombus in aneurysm growth: A computational study.

Models that seek to improve our current understanding of biochemical processes and predict disease progression have been increasingly in use over the last decades. Recently, we proposed a finite element implementation of arterial wall growth and remodeling with application to abdominal aortic aneurysms (AAAs). The study focused on changes within the aortic wall and did not include the complex role of intraluminal thrombus (ILT) during the AAA evolution. Thus, in this work, we extend the model with a gradual deposition of ILT and its mechanical influence on AAA growth. Despite neglecting the increased biochemical activity due to the presence of a proteolytically active luminal layer of ILT, and thus underestimating rupture risk potential, we show that ILT helps to slow down the growth of the aneurysm in the axial direction by redirecting blood pressure loading from the axial-radial plane to predominately radial direction. This very likely lowers rupture potential. We also show that the ratio of ILT volume to volume sac is an important factor in AAA stabilization and that fully thrombosed aneurysms could stabilize quicker and at smaller maximum diameters compared to partially thrombosed ones. Furthermore, we show that ILT formation and the associated mural stress decrease negatively impact the wall constituent production and thickness. Although further studies that include increased biochemical degradation of the wall after the formation of ILT and ILT deposition based on hemodynamics are needed, the present findings highlight the dual role an ILT plays during AAA progression.

Computed tomography imaging of macrophage phagocytic activity in abdominal aortic aneurysm.

Inflammation plays a major role in the pathogenesis of several vascular pathologies, including abdominal aortic aneurysm (AAA). Evaluating the role of inflammation in AAA pathobiology and potentially outcome in vivo requires non-invasive tools for high-resolution imaging. We investigated the feasibility of X-ray computed tomography (CT) imaging of phagocytic activity using nanoparticle contrast agents to predict AAA outcome.Methods: Uptake of several nanoparticle CT contrast agents was evaluated in a macrophage cell line. The most promising agent, Exitron nano 12000, was further characterized in vitro and used for subsequent in vivo testing. AAA was induced in Apoe-/- mice through angiotensin II (Ang II) infusion for up to 4 weeks. Nanoparticle biodistribution and uptake in AAA were evaluated by CT imaging in Ang II-infused Apoe-/- mice. After imaging, the aortic tissue was harvested and used from morphometry, transmission electron microscopy and gene expression analysis. A group of Ang II-infused Apoe-/- mice underwent nanoparticle-enhanced CT imaging within the first week of Ang II infusion, and their survival and aortic external diameter were evaluated at 4 weeks to address the value of vessel wall CT enhancement in predicting AAA outcome.Results: Exitron nano 12000 showed specific uptake in macrophages in vitro. Nanoparticle accumulation was observed by CT imaging in tissues rich in mononuclear phagocytes. Aortic wall enhancement was detectable on delayed CT images following nanoparticle administration and correlated with vessel wall CD68 expression. Transmission electron microscopy ascertained the presence of nanoparticles in AAA adventitial macrophages. Nanoparticle-induced CT enhancement on images obtained within one week of AAA induction was predictive of AAA outcome at 4 weeks.Conclusions: By establishing the feasibility of CT-based molecular imaging of phagocytic activity in AAA, this study links the inflammatory signal on early time point images to AAA evolution. This readily available technology overcomes an important barrier to cross-sectional, longitudinal and outcome studies, not only in AAA, but also in other cardiovascular pathologies and facilitates the evaluation of modulatory interventions, and ultimately upon clinical translation, patient management.

A Deep Learning Approach to Predict Abdominal Aortic Aneurysm Expansion Using Longitudinal Data

An abdominal aortic aneurysm (AAA) is a gradual enlargement of the aorta that can cause a life-threatening event when a rupture occurs. Aneurysmal geometry has been proved to be a critical factor in determining when to surgically treat AAAs, but, it is challenging to predict the patient-specific evolution of an AAA with biomechanical or statistical models. The recent success of deep learning in biomedical engineering shows promise for predictive medicine. However, a deep learning model requires a large dataset, which limits its application to the prediction of the patient-specific AAA expansion. In order to cope with the limited medical follow-up dataset of AAAs, a novel technique combining a physical computational model with a deep learning model is introduced to predict the evolution of AAAs. First, a vascular Growth and Remodeling (G&R) computational model, which is able to capture the variations of actual patient AAA geometries, is employed to generate a limited in silico dataset. Second, the Probabilistic Collocation Method (PCM) is employed to reproduce a large in silico dataset by approximating the G&R simulation outputs. A Deep Belief Network (DBN) is then trained to provide fast predictions of patient-specific AAA expansion, using both in silico data and patients' follow-up data. Follow-up Computer Tomography (CT) scan images from 20 patients are employed to demonstrate the effectiveness and the feasibility of the proposed model. The test results show that the DBN is able to predict the enlargements of AAAs with an average relative error of 3.1%, which outperforms the classical mixed-effect model by 65%.

Morphological and Biomechanical Evolution of Abdominal Aortic Aneurysms During Surveillance

Morphological and Biomechanical Evolution of Abdominal Aortic Aneurysms During Surveillance

Vertebral erosion due to chronic rupture of aneurismatic abdominal aorta

Introduction. Extremely rarely, the evolution of abdominal aortic aneurysm (AAA) includes the phase when extravasations of the blood from a ruptured aneurysm is contained by the surrounding tissue, referred to as chronic (contained) rupture of the AAA. Our aim was to call attention to this life-threatening condition, which is always challenging for diagnosis. Case outline. A 58-year-old man reported to the Emergency Center for significant abdominal pain. Ultrasound examination showed an infrarenal aneurysm of the abdominal aorta. A computed tomography scan of the thorax, abdomen, and pelvis with iodine contrast in arterial phase was performed. A free gas collection was observed between the liver and the anterior abdominal wall that is traced to a ruptured inflamed diverticulum on the transversal colon. Immediately distal to the branching sites of the renal arteries, the abdominal aorta extended forward and aneurismatically expanded. Posterior left, along the psoas muscle, a rupture of the aortic wall was seen, with an organized hematoma that accompanied the muscle. Between the hematoma and the aortic aneurysm, erosions of the anterior and lateral part of the vertebral bodies L2 and L3 were discovered. The patient underwent endovascular AAA repair (EVAR) and recovered well. Conclusion. Multidetector computed tomography angiography is a reliable, non-invasive, and necessary examination for localization and evaluation of the size of the AAA form, its chronic rupture, and complications such as vertebral body erosion.

Abdominal Aortic Aneurysm Volumetric Evaluation During Mid-term Follow-Up After Endovascular Sealing Using the Nellix™ Device.

To analyze the volumetric evolution of abdominal aortic aneurysms after endovascular sealing (EVAS) with the Nellix™ device during follow-up. Patients who underwent elective EVAS in our institution in 2014 and 2015 were retrospectively reviewed. Preoperative, postoperative and 1-year scans were processed. A custom software was conceived to assess semi-automated measurements of the aneurysm sac and the endograft sizes including volume, maximum diameter, sectional area and perimeter. Thrombus volume, aneurysm length, mean distance between the stents inside the polymer-filled sacs and endograft migration were also estimated. Manual maximum diameters were measured for comparison. Inter and intra-observer variability of the proposed semi-automated method was evaluated. Pre-EVAS, post-EVAS and last follow-up scans of 12 patients were finally analyzed during a mean follow-up of 17 ± 5months. No endograft migration or endoleak were detected. During follow-up, aneurysm volume and perimeter slightly increased compared to post-EVAS scans (+ 1 and + 5%, respectively, p < 0.05). A systematic 6% enlargement of the endobag volume was also observed (range 1-15mL, p < 0.001). Endobag maximum diameter, area and perimeter increased 4, 8, and 8%, respectively (all p < 0.01). Mean plane-by-plane distance between stents increased 4% (p < 0.05). Mean thrombus volume did not change during follow-up, although a high variability was observed. Aneurysm and thrombus volume changes were highly correlated (r = 0.93, p < 0.001). No associations were observed between aneurysm and endobag volume changes. Intra- and inter-observer variability was below 1.7 and 2.4% for diameter and volume measurements, respectively. The automated measurements of post-EVAS aneurysm diameter and volume were higher than preoperative (p < 0.05). Maximum diameters measured manually did not differ between scans. Small aneurysm volume enlargement detected during a mid-term follow-up was associated with thrombus size change, whereas systematic endograft expansion resulted independent from the aortic growth. Volumetric measurements using a semi-automated method could quantify small changes in aneurysm, endograft and thrombus sizes not detected by manually defined maximal diameters.

Exploring antibody-dependent adaptive immunity against aortic extracellular matrix components in experimental aortic aneurysms

BackgroundRecent evidence suggests that adaptive immunity develops during abdominal aortic aneurysm evolution. Uncertainties remain about the antigens implicated and their role in inducing rupture. Because antigens from the extracellular matrix (ECM) have been suspected, the aim of this experimental study was to characterize the role of adaptive immunity directed against antigens from the aortic ECM. MethodsIn a first step, an experimental model of abdominal aortic aneurysm rupture based on adaptive immunity against the ECM was developed and characterized. Forty 4-week-old male Lewis rats were divided into two groups. In the ECM group (n = 20), rats were presensitized against the guinea pig aortic ECM before implantation of a decellularized aortic xenograft (DAX). In the control group (n = 20), rats were not presensitized before DAX implantation. In each group, half the rats were sacrificed at day 3 to analyze early mechanisms involved after DAX implantation. In a second step, we aimed to assess which ECM component was most efficient in inducing rupture. For this purpose, the nonfibrillar and fibrillar ECM components were sequentially extracted from the guinea pig aortic wall. Forty Lewis rats were then divided into four groups. Each group was presensitized against one ECM component (structural glycoproteins and proteoglycans, collagen, elastin alone, and elastin-associated glycoproteins) before DAX implantation. Apart from those that experienced rupture, rats were sacrificed at day 21. Xenografts were harvested for histologic, immunofluorescence, and conditioned medium analyses. ResultsIn total, early aortic rupture occurred in 80% of the ECM group vs 0% of the control group (P < .001). In the ECM group, major circumferential immunoglobulin deposits were observed in combination with the C3 complement fraction, without cell infiltration. Conditioned medium analysis revealed that matrix metalloproteinase 9 and myeloperoxidase levels and elastase activities were significantly increased in this group. Immunofluorescence analysis demonstrated that myeloperoxidase co-localized with tissue-free DNA and histone H4, highlighting local neutrophil activation and formation of neutrophil extracellular traps. Following differential presensitization, it appeared that rats presensitized against structural glycoproteins and proteoglycans were significantly more susceptible to rupture after DAX implantation. ConclusionsStimulating adaptive immunity against the aortic ECM, especially structural glycoproteins and proteoglycans, triggers rupture after DAX implantation. Further studies are needed to assess the precise proteins involved.

Potential biomechanical roles of risk factors in the evolution of thrombus-laden abdominal aortic aneurysms.

Abdominal aortic aneurysms (AAAs) typically harbour an intraluminal thrombus (ILT), yet most prior computational models neglect biochemomechanical effects of thrombus on lesion evolution. We recently proposed a growth and remodelling model of thrombus-laden AAAs that introduced a number of new constitutive relations and associated model parameters. Because values of several of these parameters have yet to be elucidated by clinical data and could vary significantly from patient to patient, the aim of this study was to investigate the possible extent to which these parameters influence AAA evolution. Given that some of these parameters model potential effects of factors that influence the risk of rupture, this study also provides insight into possible roles of common risk factors on the natural history of AAAs. Despite geometrical limitations of a cylindrical domain, findings support current thought that smoking, hypertension, and female sex likely increase the risk of rupture. Although thrombus thickness is not a reliable risk factor for rupture, the model suggests that the presence of ILT may have a destabilizing effect on AAA evolution, consistent with histological findings from human samples. Finally, simulations support two hypotheses that should be tested on patient-specific geometries in the future. First, ILT is a potential source of the staccato enlargement observed in many AAAs. Second, ILT can influence rupture risk, positively or negatively, via competing biomechanical (eg, stress shielding) and biochemical (ie, proteolytic) effects. Although further computational and experimental studies are needed, the present findings highlight the importance of considering ILT when predicting aneurysmal enlargement and rupture risk.

Association of ficolin‐3 with abdominal aortic aneurysm presence and progression

Background Abdominal aortic aneurysm (AAA) patients are usually asymptomatic and AAA evolution is unpredictable. Ficolin-3, mainly synthesized by the liver, is a molecule of the lectin complement-activation pathway involved in AAA pathophysiology. Objectives To define extra-hepatic sources of ficolin-3 in AAA and investigate the role of ficolin-3 as a biomarker of the presence and progression of AAA. Methods Microvesicles (exosomes and microparticles) were isolated from culture-conditioned medium of ADP-activated platelets, as well as from AAA tissue-conditioned medium (thrombus and wall). Ficolin-3 levels were analyzed by western-blot, real-time PCR, immunohistochemistry and ELISA. Results Increased ficolin-3 levels were observed in microvesicles isolated from activated platelets. Similarly, microvesicles released from AAA tissue display increased ficolin-3 levels as compared with those from healthy tissue. Moreover, ficolin-3 mRNA levels in the AAA wall were greatly increased compared with healthy aortic walls. Immunohistochemistry of AAA tissue demonstrated increased ficolin-3, whereas little staining was present in healthy walls. Finally, increased ficolin-3 levels were observed in AAA patients' plasma (n = 478) compared with control plasma (n = 176), which persisted after adjustment for risk factors (adjusted odds ratio [OR], 5.29; 95% confidence interval [CI], 3.27, 8.57)]. Moreover, a positive association of ficolin-3 with aortic diameter (Rho, 0.25) and need for surgical repair was observed, also after adjustment for potential confounding factors (adjusted hazard ratio, 1.55; 95% CI, 1.11, 2.15). Conclusions In addition to its hepatic expression, ficolin-3 may be released into the extracellular medium via microvesicles, by both activated cells and pathological AAA tissue. Ficolin-3 plasma levels are associated with the presence and progression of AAA, suggesting its potential role as a biomarker of AAA.

3D analysis of vortical structures in an abdominal aortic aneurysm by stereoscopic PIV

The present work presents an experimental in vitro three-dimensional analysis of the flow dynamics in an abdominal aortic aneurysm (AAA) through stereoscopic particle image velocimetry (SPIV) measurements. The experimental set-up mimics the pathophysiological context involving a shear thinning blood analogue fluid, compliant AAA and aorto-iliac bifurcation walls and controlled inlet and outlet flow rate and pressure waveforms as well as working fluid temperature. SPIV was carefully calibrated and conducted to assess the three velocity components in the AAA volume. For the first time in the literature, the 3D vortex ring genesis, propagation, and vanishing in the AAA bulge are experimentally described and quantified. In comparison with classical 2-component PIV measurements (2C PIV), the third component of the velocity vector was shown to be of importance in such a geometry, especially, during the deceleration phase of the flow rate. The 3D velocity magnitude reached up more than 20 % of the 2D one showing that 2C PIV are definitively not accurate enough to provide a complete description of flow behaviour in an AAA. In addition to potential clinical implications of a full 3D vortex ring description in AAA evolution, the 3D in vitro experimental quantification of the flow dynamics carried out in the present study offers an interesting tool for the validation of fluid–structure interaction numerical studies dealing with AAA.

Angiotensin-Induced Abdominal Aortic Aneurysms in Hypercholesterolemic Mice: Role of Serum Cholesterol and Temporal Effects of Exposure

ObjectiveUnderstanding variations in size and pattern of development of angiotensin II (Ang II)-induced abdominal aortic aneurysms (AAA) may inform translational research strategies. Thus, we sought insight into the temporal evolution of AAA in apolipoprotein (apo)E−/− mice.ApproachA cohort of mice underwent a 4-week pump-mediated infusion of saline (n = 23) or 1500 ng/kg/min of Ang II (n = 85) and AAA development was tracked via in vivo ultrasound imaging. We adjusted for hemodynamic covariates in the regression models for AAA occurrence in relation to time.ResultsThe overall effect of time was statistically significant (p<0.001). Compared to day 7 of AngII infusion, there was no decrease in the log odds of AAA occurrence by day 14 (−0.234, p = 0.65), but compared to day 21 and 28, the log odds decreased by 9.07 (p<0.001) and 2.35 (p = 0.04), respectively. Hemodynamic parameters were not predictive of change in aortic diameter (Δ) (SBP, p = 0.66; DBP, p = 0.66). Mean total cholesterol (TC) was higher among mice with large versus small AAA (601 vs. 422 mg/ml, p<0.0001), and the difference was due to LDL. AngII exposure was associated with 0.43 mm (95% CI, 0.27 to 0.61, p<0.0001) increase in aortic diameter; and a 100 mg/dl increase in mean final cholesterol level was associated with a 12% (95% CI, 5.68 to 18.23, p<0.0001) increase in aortic diameter. Baseline cholesterol was not associated with change in aortic diameter (p = 0.86).ConclusionsThese are the first formal estimates of a consistent pattern of Ang II-induced AAA development. The odds of AAA occurrence diminish after the second week of Ang II infusion, and TC is independently associated with AAA size.

Deformation and distensibility distribution along the abdominal aorta in the presence of aneurysmal dilatation

In order to evaluate the elastic behavior of the abdominal aortic aneurysm (AAA), the distribution of aortic deformation during the cardiac cycle is measured. Moreover, the distensibility of the AAA composite structure consisting of the AAA wall and the intraluminal thrombus (ILT), as well as that of the adjacent non-aneurysmal aortic segment (NAA), are calculated. Ten patients underwent electrocardiographically-gated computed tomography. 3D-surfaces of aortic wall and lumen were reconstructed during peak-systole and end-diastole and cross-sections perpendicular to the centerline were extracted 1 mm apart. Comparison of cross-sectional areas between peak-systole and end-diastole provided the relative area change (RAC). Mean values were calculated for NAA (RACNAA), aneurysmal wall (RACWall), and aneurysmal lumen (RACLumen). Distensibility of aneurysmal and unaffected aorta was calculated using brachial blood pressure measurements (DAAA and DNAA respectively). Normalized distensibility (DNORM) of the AAA was calculated with respect to normal aortic segment distensibility and related to aneurysm size and thrombus content. A map of aortic deformation during the cardiac cycle was obtained. Differences between RACWall (median=0.7%, range=0.3-2.1%) and both RACNAA (median=2.8%, range=0.9-4.8%) and RACLumen (median=1.8%, range=0.5-3.4%) were statistically significant. DAAA (median=0.30∙10-5 Pa-1, range=0.05-0.64∙10-5 Pa-1) was lower than DNAA (median=0.43∙10-5 Pa-1, range=0.16-0.83∙10-5 Pa-1) but difference was not statistically significant. Median DNORM was 0.73 (range=0.1-3.1) and presented a significant positive correlation with AAA size and thrombus content. Aneurysmal wall deforms significantly less than non-aneurysmal wall and aneurysmal lumen, due to altered elastic properties and reduced loading. In large AAAs with larger amounts of ILT, the lumen deformation is comparable or even exceeds that of NAA and subsequently so does the distensibility of the Wall-ILT composite, an observation suggesting a thrombus cushioning effect. DNORM may provide insight in the estimation of AAA evolution and assist in rupture risk assessment.

Abstract 223: Is Oxidative Stress Important in AAA pathogenesis?

OBJECTIVE Active investigations continue to identify markers other than size that would predict a risk of abdominal aortic aneurysms (AAA) rupture. Circulating biomarkers could also indicate optimal intervals between the surveillance intervals. Finally, the identification of biomarkers also may identify potential pathogenic pathways, and thus may open possibilities for pharmacological inhibition of growth. In the search of novel biomarkers of AAA progression, serum and wall material proteins were analyzed by a differential proteomic approach. METHODS AND RESULTS The same layers of AAA wall from ruptured (rAAA) and non-ruptured AAA were incubated, and the proteins released were analyzed by 2-dimensional difference in-gel electrophoresis. Proteins from serum were analyzed and correlated with AAA annual expansion rate. Several differentially expressed proteins involved in main AAA pathological mechanisms were identified by mass spectrometry. Among the 8 proteins identified in AAA wall, peroxiredoxin-2 (PRX-2) was more permanent, which was further validated by Western blot and immunohistochemistry. We demonstrated increased PRX-2 levels in rAAA patient wall material compared with AAA subjects and also positive correlation in serum among PRX-2 and AAA diameter and annual AAA expansion rate. CONCLUSIONS Eight proteins associated with AAA pathogenesis have been identified in AAA wall by a proteomic approach. Protein profiles identified in the wall from the rAAA and the serum would appear to be a convenient monitoring tool that has the ability to be both sensitive and specific for AAAs. Among them, PRX-2 serum levels are increased in AAA patients and correlate with AAA size and growth rate, suggesting the potential use of PRX-2 as a biomarker for AAA evolution. Characterizing such diagnostic protein profiles, combined with known risk factors as well as emerging genetic data, would contribute to the long-term objective of applying effective non-surgical therapies to the treatment of small AAA disease. Larger studies are required to confirm the potential and clinical role of the identified proteins.

Abstract 282: Pattern of Development of Abdominal Aortic Aneurysms Induced by Angiotensin In Hypercholesterolemic Mice

Background Understanding the pattern of development of abdominal aortic aneurysms (AAA) may help optimize translational research strategies. Thus we sought mechanistic insight on the pattern of AAA evolution in apolipoprotein E -/- mice. Methods Fifty-nine mice underwent a 4-week pump-mediated infusion of saline (controls; n=13) or 1500 ng/kg/min of AngII (n=46), and AAA development was tracked via in vivo serial ultrasound imaging. We adjusted for hemodynamic covariates in the mixed logistic regression model for AAA occurrence in relation to time. Results The incidence of intact AAA in AngII infused mice was 59% (27/46) of which 55.6% (15/27) were small AAA and 44.4% were large AAA (1.2-1.5 vs. &gt;1.5x baseline diameter, respectively). The incidence of rupture was 22% (10/46). All large aneurysms and most ruptures occurred within the first week of AngII exposure. Subsequent aneurysms were small and evolved in the second week of AngII infusion. The overall effect of time was statistically significant (p&lt;0.001) (Figure). When compared to day 7 of the study period, there was no decrease in the log odds of AAA occurrence by day 14 (-0.234, p = 0.65). However, compared to 21 and 28 days into AngII infusion, the log odds of an AAA occurrence decreased by -9.07 (p&lt; 0.001) and -2.35 (p= 0.04), respectively (Figure). Conclusions These are the first formal estimates of the odds of AAA occurrence vis-à-vis time in the context of a consistent pattern of AAA development in this mouse model of AngII-induced AAA. They occur in the first (large AAA) and second (small AAA) weeks of AngII infusion, and the odds of occurrence diminish thereafter. These findings provide guidance for experimental strategies.

Reestablishment of the Endothelial Lining by Endothelial Cell Therapy Stabilizes Experimental Abdominal Aortic Aneurysms

Loss of the endothelium and its replacement by a thick thrombus are structural features of human abdominal aortic aneurysms (AAAs). In AAAs, the relationship between aortic diameter expansion, the presence of thrombus, and the lack of endothelial cells (ECs) remains unexplored. We hypothesized that reendothelialization by cell therapy would modulate aortic wall destruction and ultimately stabilize AAAs. We evaluated the impact of local seeding of rat aortic ECs or peripheral blood-derived outgrowth ECs on AAA evolution. Rat aortic ECs (n=30) or serum-free medium (controls; n=29) were seeded endovascularly immediately (day 0) or 14 days after surgery in the rat xenograft model. Rat aortic EC seeding prevented AAA formation and stabilized formed AAAs at 28 days (diameter increase at day 0+28, 51±6% versus 83±6%; day 14+28, -1±4% versus 22±6% in rat aortic ECs and controls, respectively; P<0.01). This stabilizing effect was associated with the reestablishment of the endothelial lining, the suspension of proteolysis, and the reconstitution of new aortic wall rich in smooth muscle cells and extracellular matrix. Transplanted rat aortic ECs did not participate directly in aortic wall repair but exerted their healing properties through paracrine mechanisms involving the upregulation of endothelium-derived stabilizing factors and the recruitment of resident vascular cells. In rats, the transplantation of outgrowth ECs (n=7) significantly reduced by 30% the progression of AAAs and restored the abluminal endothelium at 28 days compared with controls (n=9). Our study demonstrates the potential of restoring the endothelial lining to control AAA dynamics and designates ECs as an efficient therapy to stop AAA expansion.

A fluid–structure interaction-based numerical investigation on the evolution of stress, strength and rupture potential of an abdominal aortic aneurysm

An abdominal aortic aneurysm (AAA) is an irreversible dilation of the abdominal artery. Once an aneurysm is detected by doctors, clinical intervention is usually recommended. The interventions involve traditional open surgery repair and endovascular aneurysm repair with a stent graft. Both types of prophylactic procedures are expensive and not without any risk to the patient. It is very difficult to balance the risk of aneurysm repair and the chance of rupture. The reason lies in that the changing trend of characteristic physical quantities with the evolution of AAA and the mechanisms that give rise to it are still not completely clear. In this study, computational 3D patient-specific model for investigating AAA development was established based on computed tomography (CT) images. Results showed that as the aneurysm evolved, peak wall stress and time-averaged wall shear stress distribution patterns changed. The expansion of AAA wall resulted in the increment of peak stress. The AAA wall compliance not only showed different magnitudes at different cross-sections of the aneurismal body, but also changed with the development of the aneurysm. Furthermore, minimum wall strength and rupture potential index during the three stages of AAA evolution were also investigated in detail. This study might provide valuable information on how to further explore the mechanical basis and the rupture potential during AAA evolution, and that it may assist clinical diagnostic procedures and avoid the potential risk of unnecessary surgical intervention.

805 腹部大動脈瘤の増大機序理解のための流体構造連成シミュレーション(OS8-1.工学・医療工学における移動境界問題(1),OS・一般セッション講演)

805 腹部大動脈瘤の増大機序理解のための流体構造連成シミュレーション(OS8-1.工学・医療工学における移動境界問題(1),OS・一般セッション講演)

Proteomic Analysis of Polymorphonuclear Neutrophils Identifies Catalase as a Novel Biomarker of Abdominal Aortic Aneurysm: Potential Implication of Oxidative Stress in Abdominal Aortic Aneurysm Progression

Polymorphonuclear neutrophils (PMNs) play a main role in abdominal aortic aneurysm (AAA) progression. We have analyzed circulating PMNs isolated from AAA patients and controls by a proteomic approach to identify proteins potentially involved in AAA pathogenesis. PMNs from 8 AAA patients (4 large AAA >5 cm and 4 small AAA 3-5 cm) and 4 controls were analyzed by 2D differential in-gel electrophoresis. Among differentially expressed spots, several proteins involved in redox balance were identified by mass spectrometry (eg, cyclophilin, thioredoxin reductase, catalase). Diminished catalase expression and activity were observed in PMNs from AAA patients compared with controls. In contrast, PMNs from AAA patients displayed higher H(2)O(2) and myeloperoxidase levels than PMNs from controls. Moreover, a significant decrease in catalase mRNA levels was observed in PMNs after phorbol 12-myristate 13-acetate incubation. Catalase plasma levels were also decreased in large (n=47) and small (n=56) AAA patients compared with controls (n=34). We observed catalase expression in AAA thrombus and thrombus-conditioned medium, associated with PMN infiltration. Furthermore, increased H(2)O(2) levels were observed in AAA thrombus-conditioned medium compared with the media layer. Diminished catalase levels in circulating PMNs and plasma are observed in AAA patients, supporting an important role of oxidative stress in AAA evolution.