Aneurysm Model Research Articles

A novel animal model of abdominal aortic aneurysm by mechanical injury.

The present study established a novel and reproducible animal model to study abdominal aortic aneurysms. In total, 22 adult Lewis rats underwent a procedure to produce mechanical injuries at the infrarenal aorta which was opened temporarily. The aortas were injured 6 times and repaired. Those rats were divided into 2 groups and the aortic aneurysm tissue was harvested after 42 (6-week group) or 63 (9-week group) days and evaluated for the progression of aortic aneurysms. In the 6-week group, changes in the aneurysm were observed in 6/10 (60%) rats and the mean maximum diameter of the aorta demonstrated a 119% increase in size from the baseline measurement. In the 9-week group, changes in the aneurysm were observed in 8/11 (88%) rats and the mean maximum diameter of aorta demonstrated a 133% increase in size. Additional findings from the aortic aneurysm tissue were found microscopically, including the destruction of the tunica media and the elastic fiber. The present study demonstrated that this novel animal model for the development of abdominal aortic aneurysms (AAAs) produced by mechanical injury may have high reproducibility and similar gross and microscopic morphology to humans. This model could be helpful to investigate the treatment of AAAs.

The biomechanical effects of different membrane layer structures and material constitutive modeling on patient-specific cerebral aneurysms.

The prevention, control and treatment of cerebral aneurysm (CA) has become a common concern of human society, and by simulating the biomechanical environment of CA using finite element analysis (FEA), the risk of aneurysm rupture can be predicted and evaluated. The target models of the current study are mainly idealized single-layer linear elastic cerebral aneurysm models, which do not take into account the effects of the vessel wall structure, material constitution, and structure of the real CA model on the mechanical parameters. This study proposes a reconstruction method for patient-specific trilaminar CA structural modeling. Using two-way fluid-structure interaction (FSI), we comparatively analyzed the effects of the differences between linear and hyperelastic materials and three-layer and single-layer membrane structures on various hemodynamic parameters of the CA model. It was found that the numerical effects of the different CA membrane structures and material constitution on the stresses and wall deformations were obvious, but does not affect the change in its distribution pattern and had little effect on the blood flow patterns. For the same material constitution, the stress of the three-layer membrane structure were more than 10.1% larger than that of the single-layer membrane structure. For the same membrane structure, the stress of the hyperelastic material were more than 5.4% larger than that of the linear elastic material, and the displacement of the hyperelastic material is smaller than that of the linear elastic material by about 20%. And the maximum value of stress occurred in the media, and the maximum displacement occurred in the intima. In addition, the upper region of the tumor is the maximum rupture risk region for CA, and the neck of the tumor and the bifurcation of the artery are also the sub-rupture risk regions to focus on. This study can provide data support for the selection of model materials for CA simulation and analysis, as well as a theoretical basis for clinical studies and subsequent research methods.

Elucidating key immunological biomarkers and immune microenvironment dynamics in aging-related intracranial aneurysm through integrated multi-omics analysis.

The exact cause of intracranial aneurysms (IA) is still unclear. However, pro-inflammatory factors are known to contribute to IA progression. The specific changes in the immune microenvironment of IAs remain largely unexplored. This study analyzed single-cell sequencing data from a male mouse model of brain aneurysm, focusing on samples before and after elastase-induced Willis aneurysms. The data helped identify eight distinct cell subpopulations: fibroblasts, macrophages, NK cells, endothelial cells, B cells, granulocytes, and monocytes. The study also involved bulk RNA sequencing of 97 IA samples, utilizing ssGSEA and CIBERSORT algorithms for analysis. Intercellular communication among these cells was inferred to understand the immune dynamics in IA. The study found that fibroblasts and macrophages are predominant in various disease states of IA. Notably, the onset of IA was marked by a significant increase in fibroblasts and a decrease in macrophages. There was a marked increase in cellular interactions, especially involving macrophages, at the onset of the disease. Through enrichment analysis, 12 potential immunogenic biomarkers were identified. Of these, Rgs1 emerged as a critical molecule in IA formation, confirmed through secondary validation in a single-cell sequencing dataset. This comprehensive analysis of immune cell composition and intercellular communication in IA tissues highlights the significant roles of macrophages and the molecule Rgs1. These findings shed light on the physiological and pathological conditions of IA, offering new insights into its immune microenvironment.

Flow Diverter Performance Comparison of Different Wire Materials for Effective Intracranial Aneurysm Treatment.

A flow diverter (FD) is an effective method for treating wide-necked intracranial aneurysms by inducing hemodynamic changes in aneurysms. However, the procedural technique remains challenging, and it is often not performed properly in many cases of deployment or placements. In this study, three types of FDs that changed the material of the wire were prepared within the same structure. Differences in physical properties, such as before and after delivery loading stent size, radial force, and radiopacity, were evaluated. The performances in terms of deployment and trackability force were also evaluated in a simulated model using these FDs. Furthermore, changes of deployment patterns when these FDs were applied to a 3D-printed aneurysm model were determined. The NiTi FD using only nitinol (NiTi) wire showed 100% size recovery and 42% to 45% metal coverage after loading. The low trackability force (10.9 to 22.9 gf) allows smooth movement within the delivery system. However, NiTi FD cannot be used in actual surgeries due to difficulties in X-ray identification. NiTi-Pt/W FD, a combination of NiTi wire and platinum/tungsten (Pt/W) wire, had the highest radiopacity and compression force (6.03 ± 0.29 gf) among the three FDs. However, it suffered from high trackability force (22.4 to 39.9 gf) and the end part braiding mesh tended to loosen easily, so the procedure became more challenging. The NiTi(Pt) FD using a platinum core nitinol (NiTi(Pt)) wire had similar trackability force (11.3 to 22.1 gf) to NiTi FD and uniform deployment, enhancing procedural convenience. However, concerns about low expansion force (1.79 ± 0.30 gf) and the potential for migration remained. This comparative analysis contributes to a comprehensive understanding of how different wire materials influence the performance of FDs. While this study is still in its early stages and requires further research, its development has the potential to guide clinicians and researchers in optimizing the selection and development of FDs for the effective treatment of intracranial aneurysms.

Biomechanical Characterization of Abdominal Aortic Aneurysm: The Rupture Mechanism

In this work, a four-week-old male C57Bl/6 mouse model of abdominal aortic aneurysm (AAA) was developed to examine the AAA rupture mechanism. Immunofluorescence staining was adopted for quantifying the degradation of elastin, and Picrosirius Red staining was adopted for evaluating the density of collagen. Atomic force microscopy with two probe tip sizes of 5 µm and 20 nm was adopted for mechanical characterization of the AAA. The microstructure changes and stiffness changes in both AAA samples and controlled samples were inspected. The degradation of elastin, wall thickening, formation of micro vessels, and increased density of collagen were observed in the AAA samples. The AAA samples also exhibited fragmented texture from AFM scanning. The histogram of stiffness measurements of the AAA samples with a 20 nm tip demonstrated two unique peak frequencies of stiffness intervals (0–10 kPa and 40–50 kPa). The stiffer regions were correlated with the increased density of collagen, as shown in the immunofluorescence images. The softer regions, combined with the fragmented texture, could be the key index contributing to the initiation and propagation of AAA rupture. Overall, the AAA group showed a higher stiffness than the control group (50.77 ± 62.4 kPa vs. 40.6 ± 51.86 kPa). The findings from this work may help in explaining ruptures in small AAA (<5.5 mm), which account for ten percent of all AAA ruptures. Additionally, the observations in this study may help develop early detection methods and innovative treatments for AAA.

Pharmacological Inhibition of Epidermal Growth Factor Receptor Prevents Intracranial Aneurysm Rupture by Reducing Endoplasmic Reticulum Stress.

Multiple pathways and factors are involved in the rupture of intracranial aneurysms. The EGFR (epidermal growth factor receptor) has been shown to mediate inflammatory vascular diseases, including atherosclerosis and aortic aneurysm. However, the role of EGFR in mediating intracranial aneurysm rupture and its underlying mechanisms have yet to be determined. Emerging evidence indicates that endoplasmic reticulum (ER) stress might be the link between EGFR activation and the resultant inflammation. ER stress is strongly implicated in inflammation and apoptosis of vascular smooth muscle cells, both of which are key components of the pathophysiology of aneurysm rupture. Therefore, we hypothesized that EGFR activation promotes aneurysmal rupture by inducing ER stress. Using a preclinical mouse model of intracranial aneurysm, we examined the potential roles of EGFR and ER stress in developing aneurysmal rupture. Pharmacological inhibition of EGFR markedly decreased the rupture rate of intracranial aneurysms without altering the formation rate. EGFR inhibition also significantly reduced the mRNA (messenger RNA) expression levels of ER-stress markers and inflammatory cytokines in cerebral arteries. Similarly, ER-stress inhibition also significantly decreased the rupture rate. In contrast, ER-stress induction nullified the protective effect of EGFR inhibition on aneurysm rupture. Our data suggest that EGFR activation is an upstream event that contributes to aneurysm rupture via the induction of ER stress. Pharmacological inhibition of EGFR or downstream ER stress may be a promising therapeutic strategy for preventing aneurysm rupture and subarachnoid hemorrhage.

Coaxial electrospun Ag-NPs-loaded endograft membrane with long-term antibacterial function treating mycotic aortic aneurysm

The use of endovascular stent-graft has become an important option in the treatment of aortic pathologies. However, the currently used endograft membranes have limited ability to prevent bacterial colonization. This makes them unsuitable for the treatment of mycotic aneurysms, as the infection is prone to progress after endograft implantation. Moreover, even in non-mycotic aortic pathologies, endograft infections can occur in the short or long term, especially for patients with diabetes mellitus or in immune insufficiency conditions. So, this study aimed to develop a kind of Ag-NPs-loaded endograft membrane by coaxial electrospinning technique, and a series of physical and chemical properties and biological properties of the Ag-NPs-loaded membrane were characterized. Animal experiments conducted in pigs confirmed that the Ag-NPs-loaded membrane was basically non-toxic, exhibited good biocompatibility, and effectively prevented bacterial growth in a mycotic aortic aneurysm model. In conclusion, the Ag-NPs-loaded membrane exhibited good biocompatibility, good anti-infection function and slow-release of Ag-NPs for long-term bacteriostasis. Thus, the Ag-NPs-loaded membrane might hold potential for preventing infection progression and treating mycotic aortic aneurysms in an endovascular way.

A porcine model of thoracic aortic aneurysms created with a retrievable drug infusion stent graft mirrors human aneurysm pathophysiology

ObjectiveAneurysm pathophysiology remains poorly understood, in part from the disparity of murine models with human physiology and the requirement for invasive aortic exposure to apply agents used to create aneurysm models. A retrievable drug infusion stent graft (RDIS) was developed to isolate the aortic wall intraluminally for drug exposure. We hypothesized that an RDIS could deliver aneurysm-promoting enzymes to create a porcine model of thoracic aneurysms without major surgical exposure. MethodsRetrievable nitinol stent graft frames were designed with an isolated drug delivery chamber, covered with polytetrafluoroethylene, and connected to a delivery wire with a drug infusion catheter installed to the outer chamber. Institutional Animal Care and Use Committee-approved Yorkshire pigs (n = 5) underwent percutaneous access of the femoral artery, baseline aortogram and stent placement in the thoracic aorta followed by 30-minute exposure to a cocktail of elastase, collagenase, and trypsin. After aspiration of excess drug, stent retrieval, and femoral artery repair, animals were recovered, with angiograms at 1 and 4 weeks followed by explant. Histological analysis, in situ zymography, and multiplex cytokine assays were performed. ResultsThe RDIS isolated a segment of anterior aorta angiographically, while the center lumen preserved distal perfusion during drug treatment (baseline femoral mean arterial pressure, 70 ± 14 mm Hg; after RDIS, 75 ± 12; P = .55). Endovascular induction of thoracic aneurysms did not require prior mechanical injury and animals revealed no evidence of toxicity. Within 1 week, significant aneurysmal growth was observed in all five animals (1.4 ± 0.1 cm baseline to 2.9 ± 0.7 cm; P = .002) and only within the treated region of the aorta. Aneurysms persisted out to 4 weeks. Aneurysm histology demonstrated loss of elastin and collagen that was otherwise preserved in untreated aorta. Proinflammatory cytokines and increased matrix metalloproteinase activity were increased significantly within the aneurysm. ConclusionsAn RDIS achieves isolated drug delivery while preserving distal perfusion to achieve an endovascular porcine model of thoracic aneurysms without major surgery. This model may have value for surgical training, device testing, and to better understand aneurysm pathogenesis. Most important, although the RDIS was used to simulate aortic pathology, this tool offers intriguing horizons for focused therapeutic drug delivery directly to aneurysms and, more broadly, focused locoregional drug delivery to vessels and vascular beds.

Correlation of four-dimensional ultrasound strain analysis with computed tomography angiography wall stress simulations in abdominal aortic aneurysms

ObjectiveBiomechanical modeling of infrarenal aortic aneurysms seeks to predict ruptures in advance, thereby reducing aneurysm-related deaths. As individual methods focusing on strain and stress analysis lack adequate discretization power, this study aims to explore multifactorial characterization for progressive aneurysmal degeneration. The study’s objective is to compare stress- and strain-related parameters in infrarenal aortic aneurysms. MethodsTwenty-two patients with abdominal aortic aneurysms (AAAs) (mean maximum diameter, 53.2 ± 7.2 mm) were included in the exploratory study, examined by computed tomography angiography (CTA) and three-dimensional real-time speckle tracking ultrasound (4D-US). The conformity of aneurysm anatomy in 4D-US and CTA was determined with the mean point-to-point distance (MPPD). CTA was employed for each AAA to characterize stress-related indices using the semi-automated A4-clinics RE software. Five segmentations from one 4D-US examination were fused into one averaged model for strain analysis using MATLAB and the Abaqus solver. ResultsThe mean MPPD between the adjacent points of the 4D-US and CTA-derived geometry was 1.8 ± 0.4 mm. The interclass correlation coefficients for all raters and all measurements for the maximum AAA diameter in 2D, 4D ultrasound, and CTA indicate moderate to good reliability (interclass correlation coefficient1 0.69 with 95% confidence interval [CI], 0.49-0.84; P < .001). The peak wall stress (PWS) correlates fairly with the maximum AAA diameter in 2D-US (r = 0.54; P < .01) and 4D-US (r = 0.53; P < .05) and moderately strongly with the maximum exterior AAA diameter (r = 0.63; P < .01). The peak wall rupture risk index shows a strong correlation with the PWS (ρ > 0.9; P < .001) and is influenced by anatomical parameters with equal strength. Isolated observation of the intraluminal thrombus does not provide significant information in the determination of PWS. The maximum AAA diameter in 2D-US shows a fair negative correlation with the mean circumferential, longitudinal and in-plane shear strain (ρ = −0.46; r = −0.45; ρ = −0.47; P < .05 for all). The circumferential strain ratio as an indicator of wall motion heterogeneity increases with the aneurysm diameter (r = 0.47; P < .05). The direct comparison of wall strain and wall stress indices shows no quantitative correlation. ConclusionsThe strain and stress analyses provide independent biomechanical information of AAAs. At the current stage of development, the two methods are considered complementary and may optimize a more patient-specific rupture risk prediction in the future.

Development of a rat aneurysm model coexisting thin and thick walls

Development of a rat aneurysm model coexisting thin and thick walls

Similar Distribution between EPA-containing Phosphatidylcholine and Mesenchymal Stem Marker Positive Cells in the Aortic Wall of Abdominal Aortic Aneurysm Model Rat Fed a Low-EPA Content Diet.

Abdominal aortic aneurysm (AAA) is a vascular disease characterized by progressive dilation of the abdominal aorta. Previous studies have suggested that dietary components are closely associated with AAA. Among those dietary components, eicosapentaenoic acid (EPA) is considered to have suppressive effects on AAA. In the AAA wall of AAA model animals bred under EPA-rich condition, the distribution of EPA-containing phosphatidylcholine (EPA-PC) has been reported to be similar to that of the markers of mesenchymal stem cells (MSCs) and M2 macrophages. These data suggest that the suppressive effects of EPA on AAA are related to preferential distribution of specific cells in the aortic wall. However, the distribution of EPA-PC in the AAA wall of AAA model animals fed a diet containing small amounts of EPA, which has not been reported to inhibit AAA, has not yet been explored. In the present study, we visualized the distribution of EPA-PCs in the AAA wall of AAA model animals fed a diet containing small amounts of EPA (1.5% EPA in the fatty acid composition) to elucidate the vasoprotective effects of EPA. Positive areas for markers of MSCs were significantly higher in the region where EPA-PC was abundant compared to the regions where EPA-PC was weakly detected, but not for markers of M2 macrophages, matrix metalloproteinase (MMP)-2, and MMP-9. The distribution of MSC markers was similar to that of EPA-PC but not that of M2 macrophages and MMPs. These data suggest preferential incorporation of EPA into MSCs under the conditions used in this study. The incorporation of EPA into certain cells may differ according to dietary conditions, which affect the development of AAA.

A Novel Method for the Rat Model of Abdominal Aortic Aneurysm Induced by Retroperitoneal Implantation of an Osmotic Pump System With Lipopolysaccharide

Few methods can cocurrently mimic the pathological characteristics and nature history of human abdominal aortic aneurysms (AAAs), especially for the exist of the self-healing tendency of rodents. This study tested a novel method for the AAA rat model induced by retroperitoneal implantation of an osmotic pump system with lipopolysaccharide (LPS) based on the hypothesis that chronic inflammation of perivascular adipose tissue directly influenced the development and progression of AAAs. 20 male Sprague-Dawley rats (10-month-old) fed with the Paigen diet were randomly divided into 4 groups: the blank group ×2, the sham group ×4, the empty capsule group ×4, and the LPS capsule group ×10. The LPS capsule group received implantations of the ALZET® osmotic pump capsule with LPS (3.6μg/day) parallel to the abdominal aorta through a retroperitoneal approach. Two weeks later, 6 rats were randomly selected from the LPS capsule group to form the anti-inflammatory group and received implantations of another osmotic pump capsule with interleukin (IL)-10 (75ng/day) through the same approach. The changes in abdominal aortic diameter were observed by ultrasound every 2weeks, and samples were harvested for histopathologic and immunohistochemical analysis 6weeks later. Within the 6weeks after modeling, the LPS capsule group showed sustained and significant aortic dilatation (P<0.01), while the anti-inflammatory group showed a rapid and obvious shrinkage 2weeks after the IL-10 osmotic pump capsule implantation (P<0.01). The LPS capsule group presented excellent pathological mimicking of human AAAs and showed severe medial degeneration with the least elastic content among the 5 groups at the end of the sixth week (P<0.05). Notably, the anti-inflammatory group showed perfect medial preservation with the most elastic content (P<0.05) and the highest elastin/collagen ratio (P<0.01) at the end of the study. Matrix metalloproteinases (MMP) 2 and 9 and toll-like receptor 2 showed strong expression in the LPS capsule group at the end of the sixth week, which was significantly higher than that in the blank group and sham group. Interestingly, the anti-inflammatory group showed a slightly higher MMP9 expression than the LPS capsule group though there was no statistical difference between them. This novel method for the rat AAA model induced by retroperitoneal implantation of an osmotic pump capsule with LPS can concurrently mimic the histological characteristics and natural history of human AAAs. Further studies were needed to improve the osmotic pump system.

Development of a bioresorbable self-expanding microstent for interventional applications - an innovative approach for stent-assisted coiling.

Objectives Stent-assisted coiling prevents coil migration in broad-based intracranial aneurysms. So far, only permanent metal stents are approved for intracranial use. Bioresorbable stents allow a new therapeutic approach that may prevent the need for lifelong anticoagulation. We developed a neurovascular bioresorbable microstent (NBRS) and compared it in vitro to the commercial Neuroform EZ stent. Materials and Methods The self-expanding NBRS design is oriented on the Neuroform EZ stent. Poly L-lactic acid (PLLA) was used to manufacture semi-finished products in a dipping process. For the compensation of the inferior material properties of PLLA, design adjustments were made. The NBRS were cut by means of femtosecond (fs) laser and were morphologically and mechanically compared in vitro to the Neuroform EZ stent. In vitro implantation of an NBRS was performed using a complex patient-specific 3D-printed aneurysm model. In addition, an in vitro coiling procedure to assess the stent’s ability to support a coil package was conducted. Results The NBRS could be reproducibly manufactured and had high quality regarding surface morphology. The radial force at the indicated vessel diameter of 3.0 mm was slightly higher for the Neuroform EZ stent compared to the NBRS. The self-expansion ability of the NBRS could be proven. The kink behavior of the NBRS was comparable to that of the Neuroform EZ stent, so no vessel lumen size reduction is expected. The stents showed identical deformation under local compression of 25 % based on the initial diameter, resulting in maximum forces of 24 ± 5 mN (Neuroform EZ) and 8 ± 2 mN (NBRS). The implanted NBRS expanded uniformly, and proper vessel wall adaptation was observed. The NBRS has the ability to retain a coil package. Conclusion This study reported a reproducible manufacturing process for the developed NBRS as well as mechanical and morphological in vitro tests. Furthermore, successful NBRS implantation into a complex patient-specific vessel model was presented as proof of concept. The promising results of this study, also considering the commercial Neuroform EZ stent, support the idea of fully biodegradable microstents for intracranial aneurysm treatment. Key Points

Dynamic Mixed-Reality Patient-Specific Aneurysm Clipping Simulation for Two Cases-A Feasibility Study.

Intracranial aneurysm (IA) clipping is a complex neurosurgical procedure which demands advanced technology to minimize risks and maximize patient outcomes. This study aims to evaluate the feasibility of training patient-specific microsurgical clipping procedures using a mixed-reality physical neurosurgical simulator for unruptured IA. Two board-certified neurosurgeons were asked to simulate surgery in 2 patient-specific left-side unruptured middle cerebral artery-bifurcation IA models. The study was conducted in the operation theater under realistic conditions using a mixed-reality physical neurosurgical simulator. Time, procedural, and outcome-related information was collected. The participating neurosurgeons were encouraged to attempt all possible clipping strategies, even those deemed suboptimal, reporting the outcome of each strategy. Finally, to evaluate the feasibility and added value of integrating indocyanine green fluorescence angiography (ICG-FA) with the simulator, the ICG-FA videos for each clipping strategy were analyzed and compared with the reported clipping outcomes. Between 4 and 8, different clipping strategies were applied per aneurysm model; the number of strategies was higher in Patient Model 1 (6.5 ± 1.5) (more complex aneurysm) than in Patient Model 2 (5.0 ± 1.0). The clipping strategies differed between surgeons. At most, 53.5 minutes were necessary to complete each training session, but more than double the time was spent on the more complex aneurysm. Up to 53.8% (Patient Model 1) and 50% (Patient Model 2) of the attempted strategies were discarded by the neurosurgeons during the simulation. Evaluation of aneurysm occlusion through ICG-FA was specific, although sensitivity was poor. The present mixed-reality patient-specific simulator allows testing, anticipating, and discarding different aneurysm microsurgical clipping strategies regardless of the pathology complexity. Specific limitations should be considered regarding ICG-FA aneurysm inspection after clipping.

Involvement of an IgE/Mast cell/B cell amplification loop in abdominal aortic aneurysm progression.

IgE type immunoglobulins and their specific effector cells, mast cells (MCs), are associated with abdominal aortic aneurysm (AAA) progression. In parallel, immunoglobulin-producing B cells, organised in tertiary lymphoid organs (TLOs) within the aortic wall, have also been linked to aneurysmal progression. We aimed at investigating the potential role and mechanism linking local MCs, TLO B cells, and IgE production in aneurysmal progression. Through histological assays conducted on human surgical samples from AAA patients, we uncovered that activated MCs were enriched at sites of unhealed haematomas, due to subclinical aortic wall fissuring, in close proximity to adventitial IgE+ TLO B cells. Remarkably, in vitro the IgEs deriving from these samples enhanced MC production of IL-4, a cytokine which favors IgE class-switching and production by B cells. Finally, the role of MCs in aneurysmal progression was further analysed in vivo in ApoE-/- mice subjected to angiotensin II infusion aneurysm model, through MC-specific depletion after the establishment of dissecting aneurysms. MC-specific depletion improved intramural haematoma healing and reduced aneurysmal progression. Our data suggest that MC located close to aortic wall fissures are activated by adventitial TLO B cell-produced IgEs and participate to their own activation by providing support for further IgE synthesis through IL-4 production. By preventing prompt repair of aortic subclinical fissures, such a runaway MC activation loop could precipitate aneurysmal progression, suggesting that MC-targeting treatments may represent an interesting adjunctive therapy for reducing AAA progression.

Ganglioside GM3 Protects Against Abdominal Aortic Aneurysm by Suppressing Ferroptosis.

Abdominal aortic aneurysm (AAA) is a potentially life-threatening vascular condition, but approved medical therapies to prevent AAA progression and rupture are currently lacking. Sphingolipid metabolism disorders are associated with the occurrence and development of AAA. It has been discovered that ganglioside GM3, a sialic acid-containing type of glycosphingolipid, plays a protective role in atherosclerosis, which is an important risk factor for AAA; however, the potential contribution of GM3 to AAA development has not been investigated. We performed a metabolomics study to evaluated GM3 level in plasma of human patients with AAA. We profiled GM3 synthase (ST3GAL5) expression in the mouse model of aneurysm and human AAA tissues through Western blotting and immunofluorescence staining. RNA sequencing, affinity purification and mass spectrometry, proteomic analysis, surface plasmon resonance analysis, and functional studies were used to dissect the molecular mechanism of GM3-regulating ferroptosis. We conditionally deleted and overexpressed St3gal5 in smooth muscle cells (SMCs) in vivo to investigate its role in AAA. We found significantly reduced plasma levels of GM3 in human patients with AAA. GM3 content and ST3GAL5 expression were decreased in abdominal aortic vascular SMCs in patients with AAA and an AAA mouse model. RNA sequencing analysis showed that ST3GAL5 silencing in human aortic SMCs induced ferroptosis. We showed that GM3 interacted directly with the extracellular domain of TFR1 (transferrin receptor 1), a cell membrane protein critical for cellular iron uptake, and disrupted its interaction with holo-transferrin. SMC-specific St3gal5 knockout exacerbated iron accumulation at lesion sites and significantly promoted AAA development in mice, whereas GM3 supplementation suppressed lipid peroxidation, reduced iron deposition in aortic vascular SMCs, and markedly decreased AAA incidence. Together, these results suggest that GM3 dysregulation promotes ferroptosis of vascular SMCs in AAA. Furthermore, GM3 may constitute a new therapeutic target for AAA.

Establishment and Validation of an Animal Model of Abdominal Aortic Aneurysm in Beagles Through Vascular Patch Angioplasty and Elastase Infusion

To evaluate the effect of an abdominal aortic aneurysm (AAA) animal model established in beagles by way of vascular patch angioplasty combined with elastase infusion. A total of 60 beagle dogs were included in this study. Among them, 10 beagles were assigned to a control group to obtain normal abdominal aortic wall tissue, while the other 50 underwent vascular patch angioplasty combined with elastase infusion in order to establish the AAA disease model. In order to evaluate the outcome of modeling, abdominal vascular ultrasonography was performed 14 days after the modeling surgery was performed and ultrasound and computed tomographic angiography (CTA) were performed 28 days after the modeling surgery. The criterion for evaluating modeling success is that the maximum diameter of the abdominal aortic aneurysm is 50% greater than the diameter of the normal abdominal aorta below the renal artery. A total of 20 beagles of the modelling group and 5 control beagles were sacrificed 35 days after the modeling surgery and infrarenal abdominal aortic wall tissues were harvested. Then, hematoxylin and eosin (H&E) staining, Masson's trichrome staining, and elastic van Gieson (EVG) staining were conducted to observe the pathology features of abdominal aortic wall tissues. A total of 50 beagles underwent the AAA modeling procedures, with the average operative and anesthesia time being (119.4±18.9) and (137.4±15.8) minutes, respectively, the average blood loss volume being (43.6±7.7) mL, the average abdominal aorta block time being (39.7±5.3) minutes during the modeling surgery, and the average abdominal aorta diameter measured during the surgery being (6.5±0.4) mm. Intraoperative mortality was 0%. Mortality within 30 days after the surgery was 2% (1 out of the 50 beagles). Postoperative ultrasound and CTA results revealed that the success rate of AAA modeling was 100%. Pathology examination suggested that the animal model rather successfully simulated the pathophysiologic changes associated with human AAA in regard to the morphological and pathological changes. Vascular patch angioplasty combined with elastase infusion can be used to successfully establish AAA model in beagles. The AAA modeling method described in our report demonstrates stability and reliability in aneurysm formation effect and the surgical procedures are easy to replicate. The method integrates the advantages of previous animal modeling methods and can be used to study the pathogenesis of AAA.

Mechanics of ascending aortic aneurysms based on a modulus of elasticity dependent on aneurysm diameter and pressure

The mechanical stresses and strains are examined, in ascending thoracic aortic aneurysm (aTAA) models, in a patient-specific aTAA as well as in healthy thoracic aortic models, via Finite Element Analysis. The aneurysms are assumed spherical, 1.5 mm thick, with diameters between 47 mm and 80 mm, eccentrically positioned. The geometry and wall thickness distribution of the aorta along its length are based on open literature data for an average patient age of 66.25 years, accounting for the Body Surface Area (BSA) parameter. The vessel wall material is assumed isotropic and incompressible, with its Young’s modulus varying with the aneurysm diameter and the applied intraluminal pressure (120 mmHg to 240 mmHg). In the aTAAs, peak stresses were found to increase nonlinearly with aneurysm diameter (for a given pressure) tending to reach a plateau, appearing at the proximal area of the aneurysm, whereas lower stresses were found at its distal part and even smaller at the aneurysm maximum diameter. Regarding the patient-specific aTAA model, the peak stresses appeared at the distal part of the aneurysm where a tear of the intima layer was detected during surgical intervention. Peak strains exhibited for each pressure a maximum at a certain aneurysm diameter beyond which they dropped so that essentially the vessel wall’s distensibility was thus reduced. Examining more than 100 geometry cases and employing a failure stress criterion, the rupture diameter thresholds were estimated to be 65, 52.5, 50 and 47.5 mm for a pressure of 120, 160, 200 and 240 mmHg respectively.

Abstract 18373: Differential Effects of Hypertension and Aneurysm on Stiffness Properties of the Abdominal Aorta

Introduction: The serum and glucocorticoid inducible kinase-1 (SGK-1) can contribute to matrix remodeling in murine models of hypertension (HTN) and abdominal aortic aneurysm (AAA), a potential biomechanical link between these aortopathies. Utilizing aortic stiffness as a marker of pathologic remodeling. Hypothesis: We hypothesize that HTN causes an SGK-1 dependent increase in aortic stiffness to amplify AAA growth. Methods: AngiotensinII (AngII) infusion induced HTN in C57Bl/6 mice (WT;1.46mg/kg/day) with subset groups treated + periadventitial CaCl2 to induce AAA and + infusion of the specific SGK-1 inhibitor EMD638683 (2.5mg/kg/day;n=2-4 each). Abdominal aortic ultrasound was conducted on Day 0 and Day 21 to measure stiffness parameters (radial strain(RS), distensibility(D), pulse propagation velocity(PPV)). Aortic diameter (AoD) was obtained by ultrasound and systolic blood pressures (SBP) were measured by Coda tail cuff. Results: This HTN model has consistently resulted in &gt;30% increase in SBP and AAA induction did not effect SBP. Although the WT+AngII+AAA mice had 66+8% increase in AoD, dilation was not amplified beyond that of the WT+AAA mice (72+7%, p=NS). Treatment with EMD had no impact on SBP, but did significantly reduce AAA growth (WT+AAA+EMD=29+5%; WT+AngII+AAA+EMD= 24+3%), therefore despite ongoing mechanical tension, SGK-1 inhibition abrogated a pathway necessary for degenerative remodeling. Accordingly, aortic stiffness was differentially altered in HTN versus AAA. As indictors of increased stiffness, D decreased with HTN (p&lt;0.05 vs Day 0) and RS decreased with AAA (p&lt;0.05 vs Day 0), but SGK-1 inhibition had no effect, indicating that the matrix remodeling driving these mechanical parameters was not SGK-1 dependent. Conversely, PPV was increased in both aortopathies (WT+AAA, WT+AngII, WT+AngII+AAA; each p&lt;0.05 vs Day 0) but EMD infusion prevented elevation in PPV, suggesting SGK-1-dependent preservation of contractility. Conclusions: Although concurrent induction of HTN and AAA did not amplify AAA growth, these aortopathies differentially impacted aortic stiffness. Tracking PPV as an indicator of pathologic SGK-1 activity may represent a pharmacological target to abrogate dysfunctional aortic remodeling.

Positional Relationship between Two Microcatheters according to the Navigation Sequence within the Curved Vessel in Neuroendovascular Procedures.

In neuroendovascular treatment, there are many opportunities to guide multiple catheters into the intracranial blood vessels. We report the relationship between two microcatheters according to the guiding order with experimental in vitro studies. We hypothesize that in a bent blood vessel such as a paraclinoid region of the internal carotid artery, the catheter that was first guided tended to pass through the inside, and the catheter that was guided later tended to pass through the outside. The in vitro verification was performed using a microcatheter and a balloon catheter in a silicone vascular aneurysmal model. As a result, it was found that the two catheters were arranged according to our hypothesis. This finding was also observed during the actual operation of balloon-assisted coil embolization. The positional relationship between the two catheters according to the navigation order is very important, in particular during balloon-assisted coiling and stent-assisted coiling via a jailed microcatheter.