Unleashing PD-1: a duel of immunity in aortic aneurysm formation.

Aortic aneurysms, particularly abdominal aortic aneurysms (AAAs), exhibit sex differences, with higher prevalence and severity in males than females, both in humans and experimental mouse models. In fact, male sex has been considered as the most potent nonmodifiable risk factor for AAA. Currently, there are no medications approved for the treatment of aortic aneurysms, despite the high lethality of ruptured aneurysms, which account for nearly 2% of all deaths. Moreover, the underlying molecular mechanisms mediating the sexual dimorphism of aortic aneurysms remain largely unknown. In this issue of the JCI, Mu et al. revealed a mechanism by which androgens, male sex hormones, exacerbate aortic aneurysms by suppressing programmed cell death protein 1 (PD-1) expression in T cells in an aldosterone and high salt-induced aortic aneurysm mouse model.

Appropriateness of care in complex fenestrated-branched aortic endografting.

Fenestrated and branched endovascular repair of complex abdominal and thoracoabdominal aortic aneurysms is increasingly replacing open repair as the primary modality of treatment. Mid- and long-term results are encouraging and support its use in the correct settings. Nevertheless, appropriateness of indication for treatment, patient selection, and surgeon and hospital performance has not been clearly evaluated and reviewed. The objective of this review article was to identify areas in which appropriateness of care is relevant and can be optimized when considering treatment of patients with fenestrated and branched endovascular repair for complex abdominal and thoracoabdominal aortic aneurysms.

Infective native arterial aneurysms and inflammatory abdominal aortic aneurysms: An overview with a focus on emergency settings.

Infective native arterial aneurysms and inflammatory aortic aneurysms are rare but morbid pathologies seen by vascular surgeons in the emergency setting. Presentation is not always clear, and a full workup must be obtained before adopting a management strategy. Treatment is multidisciplinary and is tailored to every case based on workup findings. Imaging with computed tomography, magnetic resonance, or with fluorodeoxyglucose-positron emission tomography aids in diagnosis and in monitoring response to treatment. Open surgery is traditionally performed for definitive management. Endovascular surgery may offer an alternative treatment in select cases with acceptable outcomes. Neither technique has been proven to be superior to the other. Physicians should consider patient's anatomy, comorbidities, life expectancy, and goals of care before selecting an approach. Long-term pharmacological treatment, with antibiotics in case of infective aneurysms and immunosuppressants in case of inflammatory aneurysms, is usually required and should be managed in collaboration with infectious disease specialists and rheumatologists.

Appropriate management of the small abdominal aortic aneurysm.

There is variation in the management of small aneurysms in the United States today, with some surgeons moving forward with elective repair and others practice ongoing surveillance. Literature exists to suggest that small aneurysms are repaired at a higher rate than should be considered acceptable, and this represents a deviation from current standards of care. To best understand the optimal care of this patient population, this article aims to evaluate the current management of small aneurysms, review contemporary guidelines and the literature behind them, and assess the appropriateness of surgical management of small aneurysms.

A Mouse Abdominal Aortic Aneurysm Model by Periadventitial Calcium Chloride and Elastase Infiltration.

Abdominal aortic aneurysm (AAA) is a life-threatening disease associated with high mortality rates. It is characterized by the permanent dilation of the abdominal aorta with at least a 50% increase in arterial diameter. Various animal models of AAA have been introduced to mimic the pathophysiological changes and study the underlying mechanisms of AAA. Among these models, the calcium chloride (CaCl2)- and elastase-induced AAA models are commonly used in mice. However, these methods have certain limitations. Traditional intraluminal porcine pancreatic elastase (PPE) perfusion is associated with high technical difficulty and a high rupture rate, while periadventitial administration of PPE yields inconsistent results. In addition, the CaCl2-induced AAA model lacks human AAA features, such as atherothrombosis and aneurysm rupture. Therefore, the combined application of CaCl2 and PPE has been proposed as an approach to enhance success rates and induce greater diameter increases in AAA animal models. This manuscript presents a comprehensive protocol for establishing a mouse AAA model through periaortic infiltration of PPE and CaCl2 in the infrarenal segment of the abdominal aorta. By following this protocol, we can achieve an AAA formation rate of approximately 90% with technical simplicity and reproducibility. Further ultrasound and histological experiments confirm that this model effectively replicates the morphological and pathological changes observed in human AAA.

Integrative analysis of single-Cell RNA sequencing and experimental validation in the study of abdominal aortic aneurysm progression.

BACKGROUND: Abdominal aortic aneurysm (AAA) is a complex vascular disorder characterized by the progressive dilation of the abdominal aorta, with a high risk of rupture and mortality. Understanding the cellular interactions and molecular mechanisms underlying AAA development is critical for identifying potential therapeutic targets. METHODS: This study utilized datasets GSE197748, GSE164678 and GSE183464 from the GEO database, encompassing bulk and single-cell RNA sequencing data from AAA and control samples. We performed principal component analysis, differential expression analysis, and functional enrichment analysis to identify key pathways involved in AAA. Cell-cell interactions were investigated using CellPhoneDB, focusing on fibroblasts, vascular smooth muscle cells (VSMCs), and macrophages. We further validated our findings using a mouse model of AAA induced by porcine pancreatic enzyme infusion, followed by gene expression analysis and co-immunoprecipitation experiments. RESULTS: Our analysis revealed significant alterations in gene expression profiles between AAA and control samples, with a pronounced immune response and cell adhesion pathways being implicated. Single-cell RNA sequencing data highlighted an increased proportion of pro-inflammatory macrophages, along with changes in the composition of fibroblasts and VSMCs in AAA. CellPhoneDB analysis identified critical ligand-receptor interactions, notably collagen type I alpha 1 chain (COL1A1)/COL1A2-CD18 and thrombospondin 1 (THBS1)-CD3, suggesting complex communication networks between fibroblasts and VSMCs. In vivo experiments confirmed the upregulation of these genes in AAA mice and demonstrated the functional interaction between COL1A1/COL1A2 and CD18. CONCLUSION: The interaction between fibroblasts and VSMCs, mediated by specific ligand-receptor pairs such as COL1A1/COL1A2-CD18 and THBS1-CD3, plays a pivotal role in AAA pathogenesis.

Mesenchymal stromal cell-derived exosomes protect against abdominal aortic aneurysm formation through CD74 modulation of macrophage polarization in mice.

BACKGROUND: Mesenchymal stromal cell (MSC)-derived exosomes (MSC-Exo) have been recognized for their significant role in regulating macrophage polarization, a process crucial to the pathogenesis of abdominal aortic aneurysm (AAA). However, the therapeutic effects of MSC-Exo on AAA remain largely unexplored. Therefore, this study aimed to investigate the functional and mechanistic aspects of MSC-Exo in the progression of AAA. METHODS: The MSC-derived exosomes were characterized using Transmission Electron Microscopy, Nanoparticle Tracking Analysis, and Western blotting. An experimental mouse model of AAA was established through the administration of angiotensin II (Ang II) in male apoe-/- mice and calcium chloride (CaCl2) in male C57/B6 mice, with subsequent tail vein injection of exosomes to evaluate their efficacy against AAA. Macrophage polarization was assessed using immunofluorescence staining and WB analysis. Mechanistic analysis was performed using 4D Label-free Proteomics analysis. RESULTS: We found that intravenous administration of MSC-Exo induced M2 polarization of macrophages within an inflammatory environment, effectively impeding AAA development in Ang II or CaCl2-induced AAA model. The therapeutic efficacy of MSC-Exo treatment was dependent on the presence of macrophages. Mechanistically, MSC-Exo suppressed the levels of cluster of differentiation 74 (CD74), modulating macrophage polarization through the TSC2-mTOR-AKT pathway. These findings highlight the potential of MSC-Exo as a therapeutic strategy for AAA by modulating macrophage polarization.

Effects of moderate doses of ionizing radiation on experimental abdominal aortic aneurysm.

BACKGROUND: Exposure to ionizing radiation has been linked to cardiovascular diseases. However, the impact of moderate doses of radiation on abdominal aortic aneurysm (AAA) remains unknown. METHODS: Angiotensin II-infused Apoe-/- mice were irradiated (acute, 1 Gray) either 3 days before (Day-3) or 1 day after (Day+1) pomp implantation. Isolated primary aortic vascular smooth muscle cells (VSMCs) were irradiated (acute 1 Gray) for mechanistic studies and functional testing in vitro. RESULTS: Day-3 and Day+1 irradiation resulted in a significant reduction in aorta dilation (Control: 1.39+/-0.12; Day-3: 1.12+/-0.11; Day+1: 1.15+/-0.08 mm, P<0.001) and AAA incidence (Control: 81.0%; Day-3: 33.3%, Day+1: 53.3%) compared to the non-irradiated group. Day-3 and Day+1 irradiation led to an increase in collagen content in the adventitia (Thickness control: 23.64+/-2.9; Day-3: 54.39+/-15.5; Day+1 37.55+/-10.8 mm, P = 0.006). However, the underlying protective mechanisms were different between Day-3 and Day+1 groups. Irradiation before Angiotensin II (AngII) infusion mainly modulated vascular smooth muscle cell (VSMC) phenotype with a decrease in contractile profile and enhanced proliferative and migratory activity. Irradiation after AngII infusion led to an increase in macrophage content with a local anti-inflammatory phenotype characterized by the upregulation of M2-like gene and IL-10 expression. CONCLUSION: Moderate doses of ionizing radiation mitigate AAA either through VSCM phenotype or inflammation modulation, depending on the time of irradiation.

Abdominal aneurysm sac thrombus CT density and volume after EVAR: which association with underlying endoleak?

BACKGROUND: Our aim was to analyse abdominal aneurysm sac thrombus density and volume on computed tomography (CT) after endovascular aneurysm repair (EVAR). METHODS: Patients who underwent EVAR between January 2005 and December 2010 and had at least four follow-up CT exams available over the first five years of follow-up were included in this retrospective single-centre study. Thrombus density and aneurysm sac volume were calculated on unenhanced CT scans. Linear mixed models were used for data analysis. RESULTS: Out of 82 patients, 44 (54%) had an endoleak on post-EVAR contrast-enhanced CT. Thrombus density significantly increased over time in both the endoleak and non-endoleak groups, with a slope of 0.159 UH/month (95% confidence interval [CI] 0.115-0.202), p < 0.0001) and 0.052 UH/month (95% CI 0.002-0.102, p = 0.041). In patients without endoleak, a significant decrease in aneurysm sac volume was identified over time (slope -0.891 cc/month, 95% CI -1.200 to -0.581); p < 0.001) compared to patients with endoleak (slope 0.284 cc/month, 95% CI -0.031 to 0.523, p = 0.082). The association between thrombus density and aneurysm sac volume was positive in the endoleak group (slope 1.543 UH/cc, 95% CI 0.948-2.138, p < 0.001) and negative in the non-endoleak group (slope -1.450 UH/cc, 95% CI -2.326 to -0.574, p = 0.001). CONCLUSION: We observed a progressive increase in thrombus density of the aneurysm sac after EVAR in patients with and without endoleak, more pronounced in patients with endoleak. The association between aneurysm volume and thrombus density was positive in patients with and negative in those without endoleak. RELEVANCE STATEMENT: A progressive increase in thrombus density and volume of abdominal aortic aneurysm sac on unenhanced CT might suggest underlying endoleak lately after EVAR. KEY POINTS: Thrombus density of the aneurysm sac after EVAR increased over time. Progressive increase in thrombus density was significantly associated to the underlying endoleak. The association between aneurysm volume and thrombus density was positive in patients with and negative in those without endoleak.

Tea polyphenol nanoparticles enable targeted siRNA delivery and multi-bioactive therapy for abdominal aortic aneurysms.

Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease, while there is a lack of pharmaceutical interventions to halt AAA progression presently. To address the multifaceted pathology of AAA, this work develops a novel multifunctional gene delivery system to simultaneously deliver two siRNAs targeting MMP-2 and MMP-9. The system (TPNs-siRNA), formed through the oxidative polymerization and self-assembly of epigallocatechin gallate (EGCG), efficiently encapsulates siRNAs during self-assembly. TPNs-siRNA safeguards siRNAs from biological degradation, facilitates intracellular siRNA transfection, promotes lysosomal escape, and releases siRNAs to silence MMP-2 and MMP-9. Additionally, TPNs, serving as a multi-bioactive material, mitigates oxidative stress and inflammation, fosters M1-to-M2 repolarization of macrophages, and inhibits cell calcification and apoptosis. In experiments with AAA mice, TPNs-siRNA accumulated and persisted in aneurysmal tissue after intravenous delivery, demonstrating that TPNs-siRNA can be significantly distributed in macrophages and VSMCs relevant to AAA pathogenesis. Leveraging the carrier's intrinsic multi-bioactive properties, the targeted siRNA delivery by TPNs exhibits a synergistic effect for enhanced AAA therapy. Furthermore, TPNs-siRNA is gradually metabolized and excreted from the body, resulting in excellent biocompatibility. Consequently, TPNs emerges as a promising multi-bioactive nanotherapy and a targeted delivery nanocarrier for effective AAA therapy.

Causal relationship between gut microbiota, plasma metabolites, inflammatory cytokines and abdominal aortic aneurysm: a Mendelian randomization study.

BACKGROUND: Complex interconnections are evident among gut microbiota, circulating metabolites, inflammatory cytokines, and the pathogenesis of abdominal aortic aneurysms (AAA), with the causal dynamics yet to be comprehensively elucidated. The primary objective of this study was to elucidate the potential causal relationships involving gut microbiota-mediated plasma metabolites, inflammatory cytokines, and AAA. METHODS: We utilized data from genome-wide association studies predominantly comprising individuals of European ancestry, encompassing four major gut microbiota signatures, 233 plasma metabolite signatures (N = 136,016), 91 inflammatory cytokine signatures (N = 14,824), and AAA signatures (N = 1,458,875). Mendelian randomization (MR), employed in a two-sample format, was utilized as a tool to investigate the potential causal pathways from gut microbiota to the development of AAA. Additionally, a two-step MR approach was employed to dissect the impact of plasma metabolites and inflammatory cytokines on the relationship between gut microbiota and AAA and to ascertain the mediated fractions. RESULTS: Our findings indicate that five phylum or family-identical bacteria, 175 plasma metabolites, and seven inflammatory factors are causally associated with AAA. Among them, five bacterial species from the same phylum or family, identified from different GWAS data, were strongly associated with AAA. Of these, two exhibited negative causality and three exhibited positive causality. We found that the phylum Firmicutes and the families Oscillospiraceae might reduce the risk of AAA, whereas the families Prevotellaceae, Sutterellaceae, and Aminobacteriaceae might increase the risk of AAA. Further screening indicated that phylum Firmicutes id.1672 (GCST90017114) may confer a protective effect against AAA by reducing triglyceride levels in medium/small high-density lipoprotein (HDL). CONCLUSION: MR analysis has delineated a causal pathway from gut microbiota, through plasma circulating metabolites and inflammatory cytokines, to the pathogenesis of AAA. The role of intestinal flora and certain biomarkers may provide a reference for the diagnosis of AAA, and contribute to the prevention, diagnosis, and treatment of AAA disease.

Regulation of matrix reloading by tumor endothelial marker 1 protects against abdominal aortic aneurysm.

Tumor endothelial marker 1 (TEM1), an activated mesenchymal cell marker, is implicated in tissue remodeling and repair. Herein, we investigated the role and therapeutic implications of TEM1 in abdominal aortic aneurysm (AAA), a potentially life-threatening aortic disease characterized by vascular inflammation and matrix turnover. Characterization of human AAA revealed increased TEM1 expression derived mainly from medial vascular smooth muscle cells (VSMCs) and adventitial fibroblasts. Bioinformatics analysis demonstrated the association between TEM1-expressing VSMCs and fibroblasts and collagen gene expression. Consistently, collagen content and TEM1 expressed by VSMCs and fibroblasts were increased during CaCl2-induced AAA formation in mice. TEM1 silencing in VSMCs and fibroblasts inhibited transforming growth factor-ß1-induced phenotypic change, SMAD2 phosphorylation, and COL1A1 gene expression. Also, Tem1 deficiency reduced collagen synthesis and exacerbated CaCl2-induced AAA formation in mice without disturbing elastin destruction and inflammatory responses. In contrast, rTEM1 promoted phenotypic change and COL1A1 gene expression through SMAD2 phosphorylation in VSMCs and fibroblasts. Treatment with rTEM1 enhanced collagen synthesis, attenuated elastin fragmentation, and inhibited CaCl2-induced and angiotensin II-infused AAA formation. In summary, TEM1 in resident stromal cells regulates collagen synthesis to counteract aortic wall failure during AAA formation. Matrix integrity restored by rTEM1 treatment may hold therapeutic potential against AAA.

Haemodynamic effects of non-Newtonian fluid blood on the abdominal aorta before and after double tear rupture.

OBJECTIVES: Intimal tears caused by aortic dissection can weaken the arterial wall and lead to aortic aneurysms. However, the effect of different tear states on the blood flow behaviour remains complex. This study uses a novel approach that combines numerical haemodynamic simulation with in vitro experiments to elucidate the effect of arterial dissection rupture on the complex blood flow state within the abdominal aneurysm and the endogenous causes of end-organ malperfusion. MATERIALS AND METHODS: Based on the CT imaging data and clinical physiological parameters, the overall arterial models including aortic dissection and aneurysm with single tear and double tear were established, and the turbulence behaviours and haemodynamic characteristics of arterial dissection and aneurysm under different blood pressures were simulated by using non-Newtonian flow fluids with the pulsatile blood flow rate of the clinical patients as a cycle, and the results of the numerical simulation were verified by in vitro simulation experiments. RESULTS: Hemodynamic simulations revealed that the aneurysm and single-tear false lumen generated a maximum pressure of 320.591 mmHg, 267 % over the 120 mmHg criterion. The pressure differential generates reflux, leading to a WSS of 2247.9 Pa at the TL inlet and blood flow velocities of up to 6.41 m/s inducing extend of the inlet. DTD Medium FL instantaneous WP above 120 mmHg Standard 151 % Additionally, there was 82.5 % higher flow in the right iliac aorta than in the left iliac aorta, which triggered malperfusion. Thrombus was accumulated distal to the tear and turbulence. These results are consistent with the findings of the in vitro experiments. CONCLUSIONS: This study reveals the haemodynamic mechanisms by which aortic dissection induces aortic aneurysms to produce different risk states. This will contribute to in vitro simulation studies as a new fulcrum in the process of moving from numerical simulation to clinical trials.

[Abdominal aortic malformation in 2 dogs]. / Abdominale Aortenmalformation bei 2 Hunden.

Aneurysms of the abdominal aorta are only sporadically documented in the veterinary literature. This publication describes 2 canine cases in which abdominal aortic malformation was detected by sonography and confirmed by computed tomography. In one case a histological diagnosis of an aortic aneurysm was possible.One dog showed posterior weakness, in the second dog the aortic aneurysm had been noticed sonographically during a routine examination.In the patient with the proven aortic aneurysm, it may be presumed that a hemodynamically relevant component in consequence to the altered flow profile and occurring turbulence exists. In accordance with human medical standards, regular monitoring of these patients, both clinically and by ultrasound, would therefore appear to be useful in order to be able to detect the occurrence or progression of secondary hemodynamic changes and possible thrombus formation at an early stage. In contrast, the second case presented here has not shown any clinical signs with regard to the abdominal vascular malformation up to the present time.

Circulating monocyte populations as biomarker for abdominal aortic aneurysms: a single-center retrospective cohort study.

Background: Abdominal aortic aneurysm (AAA) development is driven by inflammation, in particular myeloid cells, which represent attractive biomarker candidates. Yet to date, the maximum aortic diameter is the only clinically applied predictor of AAA progression and indicator for surgical repair. We postulated that aortic inflammation is reflected in a systemic change of monocyte populations, which we investigated regarding marker potential in AAA diagnosis and prognosis. Methods: We conducted a single-center retrospective cohort study in a diagnostic setting, measuring monocyte subsets by flow cytometry in peripheral blood samples of 47 AAA patients under surveillance, matched with 25 healthy controls and 25 patients with peripheral artery disease (PAD). In a prognostic setting, we acquired longitudinal data of 60 AAA patients including aneurysm growth assessment by computed tomography at 6-month intervals. Results: Blood levels of total monocytes, CD16+ monocytes and particularly intermediate monocytes were significantly increased in AAA patients versus healthy individuals and were also elevated compared to PAD patients. The combination of intermediate monocyte and D-dimer blood levels outperformed the individual diagnostic marker values. Additionally, the elevated concentrations of total monocytes, intermediate monocytes, and monocyte-platelet aggregates (MPA) were suited to predict rapid AAA progression over short-term periods of six months. Of note, MPA were identified as independent predictor of AAA disease progression in multivariable analysis. Conclusion: Circulating monocyte subsets are elevated in AAA patients and support diagnosis and prediction of aneurysm progression. Monocyte subsets and D-dimer reflect different hallmarks (inflammation and hemostasis) of AAA pathology and when combined, may serve as improved biomarker.

Ruptured AAA: bridging the gap between international guidelines and local clinical realities.

BACKGROUND: Treatment of asymptomatic Abdominal Aortic Aneurysms (AAA) presents a clinical challenge, requiring a delicate balance between rupture risk, patient comorbidities, and intervention-related complications. International guidelines recommend intervention for specific AAA size thresholds, but these are based on historical trials with limited female representation. We aimed to analyse disease characteristics, AAA size at rupture, and intervention outcomes in patients with ruptured AAA from 2009 to 2023 to investigate the gap between guidelines and local realities. METHODS: This single-centre retrospective cohort study analysed electronic health records of patients treated for a ruptured AAA, excluding those who were managed palliatively. The study assessed patients' demographics, risk factors, comorbidities, clinical presentation, radiological characteristics, and outcomes. RESULTS: Of 164 patients (41 females, 123 males, median age 73.5), 93.3% presented with abdominal or back pain. The median AAA size at rupture was 8.0 cm in males and 7.6 cm in females. No significant correlations were found between demographic characteristics, risk factors, AAA size, repair modality, and outcomes. Trends show a decline in AAA prevalence and rupture rates, aligning with global health initiatives. Post-intervention survival rates at 30 days were 70.7% (67.5% in males and 80.0% in females), and at 2 years were 65.85% (61.7% in males and 70.0% in females). CONCLUSION: Evolving AAA trends and improved post-intervention survival rates warrant a critical reassessment of existing intervention recommendations. Adjusting intervention thresholds to larger sizes may be justified to optimise the risk-benefit ratio.

Investigating the association between gut microbiome and aortic aneurysm diseases: a bidirectional two-sample Mendelian randomization analysis.

Objective: This study aims to investigate the associations between specific bacterial taxa of the gut microbiome and the development of aortic aneurysm diseases, utilizing Mendelian Randomization (MR) to explore these associations and overcome the confounding factors commonly present in observational studies. Methods: Employing the largest available gut microbiome and aortic aneurysm Genome-Wide Association Study databases, including MiBioGen, Dutch Microbiome Project, FinnGen, UK Biobank, and Michigan Genomics Initiative, this study performs two-sample bidirectional MR analyses. Instrumental variables, linked to microbiome taxa at significant levels, were selected for identifying relationships with abdominal aortic aneurysms (AAA), thoracic aortic aneurysms (TAA), and aortic dissection (AD). Methods like inverse variance weighted, MR-PRESSO, MR-Egger, weighted median, simple mode, and mode-based estimate were used for MR analysis. Heterogeneity was assessed with the Cochran Q test. MR-Egger regression and MR-PRESSO addressed potential unbalanced horizontal pleiotropy. Results: The analysis did not find any evidence of statistically significant associations between the gut microbiome and aortic aneurysm diseases after adjusting for the false discovery rate (FDR). Specifically, while initial results suggested correlations between 19 taxa and AAA, 25 taxa and TAA, and 13 taxa with AD, these suggested associations did not hold statistical significance post-FDR correction. Therefore, the role of individual gut microbial taxa as independent factors in the development and progression of aortic aneurysm diseases remains inconclusive. This finding underscores the necessity for larger sample sizes and more comprehensive studies to further investigate these potential links. Conclusion: The study emphasizes the complex relationship between the gut microbiome and aortic aneurysm diseases. Although no statistically significant associations were found after FDR correction, the findings provide valuable insights and highlight the importance of considering gut microbiota in aortic aneurysm diseases research. Understanding these interactions may eventually contribute to identifying new therapeutic and preventive strategies for aortic aneurysm diseases.

Advanced Abdominal Aortic Aneurysm Modeling in Mice by Combination of Topical Elastase and Oral ß-aminopropionitrile.

The topical elastase murine model of abdominal aortic aneurysm (AAA) is enhanced when combined with ß-aminopropionitrile (BAPN)-supplemented drinking water to reliably produce true infrarenal aneurysms with behaviors that mimic human AAAs. Topically applying elastase to the adventitia of the infrarenal aorta causes structural damage to the elastic layers of the aortic wall and initiates aneurysmal dilation. Co-administering BAPN, a lysyl oxidase inhibitor, promotes sustained wall degeneration by reducing collagen and elastin crosslinking. This combination results in large AAAs that progressively expand, form intraluminal thrombus, and are capable of rupture. Refining surgical techniques, such as circumferentially isolating the entire infrarenal aortic segment, can help standardize the procedure for a consistent and thorough application of porcine pancreatic elastase despite different operators and anatomic variations between mice. Therefore, the elastase/BAPN model is a refined approach to surgically inducing AAA in mice, which may better recapitulate human aneurysms and provide additional opportunities to study aneurysm growth and rupture risk.

Explantador de Cabrera: un nuevo dispositivo para explantar endoprótesis aórticas después de reparo endovascular de aneurisma de aorta, un estudio experimental ex vivo / Cabrera explanter: a new device to explant aortic stents after endovascular aortic aneurysm repair, an ex vivo experimental study

Introducción. Las complicaciones posteriores a la reparación endovascular de aneurisma (EVAR) pueden resolverse con técnicas endovasculares. Sin embargo, cuando está indicada, la explantación de una endoprótesis es un procedimiento complejo, que se asocia a lesiones vasculares o viscerales, con alta morbimortalidad, en pacientes con edad avanzada y múltiples comorbilidades, y por lo tanto, alto riesgo quirúrgico. No existen dispositivos producidos por la industria para explantar las endoprótesis aórticas, por lo que el objetivo de este trabajo fue desarrollar un dispositivo para la explantación de endoprótesis aórticas. Métodos. Se llevó a cabo un estudio experimental, en fase preclínica, para desarrollar un dispositivo para la explantación de endoprótesis aórticas, con pruebas en modelos 3D y en un modelo animal porcino cadavérico. Resultados. Es factible desarrollar un modelo experimental de un nuevo dispositivo para explantar endoprótesis aórticas, denominado explantador de Cabrera, y comprobar su funcionamiento en un modelo animal cadavérico. El uso del explantador de Cabrera limitó el daño de la pared aórtica por parte de la endoprótesis en un 100 % al momento de su explantación en un modelo experimental ex vivo. Conclusión. Usando una jeringa septo, el explantador de Cabrera es superior a la técnica estándar de explantación de una endoprótesis al limitar la lesión de la pared aórtica, al colapsar y liberar los ganchos de fijación suprarrenal de forma controlada y segura al interior de la luz aórtica y, posteriormente, extraerla de forma rápida y efectiva, conservando la mayor cantidad de aorta sana para la posterior reconstrucción aorto-ilíaca.

Introduction. Complications after endovascular aneurysm repair (EVAR) can be resolved with endovascular techniques; however, when indicated, stent explantation is a complex procedure, which is associated with vascular or visceral injuries, with high morbidity and mortality in patients, with advanced age and multiple comorbidities, and therefore high surgical risk. There are no devices produced by the industry to explant aortic endoprostheses, so the objective of this work was to develop a device for the explantation of aortic endoprostheses. Methods. An experimental study was carried out, in the preclinical phase, to develop a device for the explantation of aortic endoprostheses, with tests in 3D models and in a cadaveric porcine animal model. Results. It is feasible to develop an experimental model of a new device for explanting aortic endoprostheses, called Cabrera explanter, and verify its operation in a cadaveric animal model. The use of the Cabrera explanter limited damage to the aortic wall by the endoprosthesis by 100% at the time of explantation in an ex vivo experimental model. Conclusions. Using a septum syringe, the Cabrera explanter is superior to the standard stent explantation technique by limiting injury to the aortic wall, collapsing and releasing the adrenal fixation hooks in a controlled and safe manner into the aortic lumen, and subsequently, extract it quickly and effectively, preserving the greatest amount of healthy aorta for the subsequent aorto-iliac reconstruction.