To improve abdominal aortic aneurysm (AAA) rupture risk assessment, a large, longitudinal study on AAA hemodynamics and biomechanics is necessary, using personalized fluid-structure interaction (FSI) modeling. 3-dimensional, time-resolved ultrasound (3D+t US) is the preferred image modality to obtain the patient-specific AAA geometry for such a study, since it is safe, affordable and provides temporal information. However, the 3D+t US field-of-view (FOV) is limited and therefore often fails to capture the inlet and aorto-iliac bifurcation geometry. In this study, a framework was developed to add parametric inlet and bifurcation geometries to the abdominal aortic aneurysm geometry by employing dataset statistics and parameters of the AAA geometry. The impact of replacing the patient-specific inlet and bifurcation geometries, acquired using computed tomography (CT) scans, by parametric geometries was evaluated by examining the differences in hemodynamics (systolic and time-averaged wall shear stress and oscillatory shear index) in the aneurysm region. The results show that the inlet geometry has a larger effect on the AAA hemodynamics (median differences of 7.5 to 18.8%) than the bifurcation geometry (median differences all below 1%). Therefore, it is not feasible to replace the patient-specific inlet geometry by a generic one. Future studies should investigate the possibilities of extending the proximal FOV of 3D+t US. However, this study did show the feasibility of adding a parametric bifurcation geometry to the aneurysm geometry. After extending the proximal FOV, the obtained framework can be used to extract AAA geometries from 3D+t US for FSI simulations, despite the absence of the bifurcation geometry.

Macrophages play crucial roles in abdominal aortic aneurysm (AAA) formation through the inflammatory response and extracellular matrix degradation; therefore, regulating macrophages may suppress AAA formation. Interleukin-38 (IL-38) is a member of the IL-1 family, which binds to IL-36 receptor (IL1RL2) and has an anti-inflammation effect. Because macrophages express IL1RL2, we hypothesized that IL-38 suppresses AAA formation by controlling macrophages. We assessed a C57BL6/J mouse angiotensin II-induced AAA model with or without IL-38 treatment. RAW 264.7 cells were cultured with tumor necrosis factor-α and treated with or without IL-38. Because p38 has important roles in inflammation, we assessed p38 phosphorylation in vitro and in vivo. To clarify whether the IL-38 effect depends on the p38 pathway, we used SB203580 to inhibit p38 phosphorylation. IL1RL2+ macrophage accumulation along with matrix metalloproteinase (MMP)-2 and -9 expression was observed in mouse AAA. IL-38 reduced the incidence of AAA formation along with reduced M1 macrophage accumulation and MMP-2 and -9 expression in the AAA wall. Macrophage activities including inducible nitric oxide, MMP-2, and MMP-9 production and spindle-shaped changes were significantly suppressed by IL-38. Furthermore, we revealed that inhibition of p38 phosphorylation diminished the effects of IL-38 on regulating macrophages to reduce AAA incidence, indicating the protective effects of IL-38 depend on the p38 pathway. IL-38 plays protective roles against AAA formation through regulation of macrophage accumulation in the aortic wall and modulating the inflammatory phenotype. Using IL-38 may be a novel therapy for AAA patients.

In the cardiovascular diseased (CVD) conditions, it is essential to choose a suitable rheological model for capturing the correct physics behind the hemodynamic in the multiply afflicted diseased arterial network. This study investigates the effect of blood rheology on hemodynamics in a blood vessel with abdominal aortic aneurysm (AAA) and right internal iliac stenosis (RIIAS). A model with AAA and RIIAS is reconstructed from a human subject's computed tomography (CT) data. Localized mesh generation and pulsatile inflow condition are considered. Non-Newtonian models such as the Power-law, Carreau, Cross, and Herschel Berkley models are used in simulations. The outcome from a validated computational model is compared with the Newtonian model to identify the suitable model for dealing with pathological complications under consideration. The capabilities and significance of various rheological models are also examined via Wall Pressure (WP), Wall Shear Stress (WSS), velocity, Global non-Newtonian importance factor (IG), Vorticity Streamlines, and Swirling Strength. It is noted that during the entire cardiac cycle, the IG factor of the cross model is found to be relatively more significant. Power Law depicts larger IG factor during peak systole and early diastole. Also, the cross model depicts larger WSS, WPS, swirling strength distribution and vorticity during the peak systolic and diastolic phases It is noted that IG ∼0.02 is an appropriate non-Newtonian blood activity cut-off value in the descending abdominal artery having AAA and RIIAS. The critical important WSS values are in the range of 0-9 Pa which is stated in WSS contour plot.

Obstruction of the duodenum by an abdominal aortic aneurysm (AAA) (aortoduodenal syndrome) has rarely been reported. It presents with symptoms of upper gastrointestinal (GI) tract obstruction. Obstructive jaundice caused by an AAA is also extremely rare and requires high clinical suspicion. We present a unique case with informed consent of an elderly gentleman who presented with both rare presentations over a course of few months. After extensive literature search, we have found case reports of patients showing either of the two unusual presentations, but none were found to show them together.

Abdominal aortic aneurysm (AAA) is pathologically characterized by intimal atherosclerosis, disruption and attenuation of the elastic media, and adventitial inflammatory infiltrates. Although all these pathological events are possibly involved in the pathogenesis of AAA, the functional roles contributed by adventitial inflammatory macrophages have not been fully documented. Recent studies have revealed that increased expression of matrix metalloproteinase-12 (MMP-12) derived from macrophages may be particularly important in the pathogenesis of both atherosclerosis and AAA. In the current study, we developed a carrageenan-induced abdominal aortic adventitial inflammatory model in hypercholesterolemic rabbits and evaluated the effect of adventitial macrophage accumulation on the aortic remodeling with special reference to the influence of increased expression of MMP-12. To accomplish this, we compared the carrageenan-induced aortic lesions of transgenic (Tg) rabbits that expressed high levels of MMP-12 in the macrophage lineage to those of non-Tg rabbits. We found that the aortic medial and adventitial lesions of Tg rabbits were greater in degree than those of non-Tg rabbits, with the increased infiltration of macrophages and prominent destruction of elastic lamellae accompanied by the frequent appearance of dilated lesions, while the intimal lesions were slightly increased. Enhanced aortic lesions in Tg rabbits were focally associated with increased dilation of the aortic lumens. RT-PCR and Western blotting revealed high levels of MMP-12 in the lesions of Tg rabbits that were accompanied by elevated levels of MMP-2 and -3, which was caused by increased number of macrophages. Our results suggest that adventitial inflammation constitutes a major stimulus to aortic remodeling and increased expression of MMP-12 secreted from adventitial macrophages plays an important role in the pathogenesis of vascular diseases such as AAA.

Introduction: Chronic heart disease (CHD) is a common comorbidity of patients receiving endovascular aneurysm repair (EVAR) for abdominal aortic aneurysms (AAA). The explicit relationship between ventricular systolic function and EVAR complication of thrombotic events is unknown. Methods: In this study, we proposed a three-dimensional numerical model coupled with the lumped-elements heart model, which is capable of simulating thrombus formation in diverse systolic functions. The relation of cardiac functions and the predicted risk of thrombus formation in the aorta and/or endograft of 4 patients who underwent EVAR was investigated. Relative risks for thrombus formation were identified using machine-learning algorithms. Results: The computational results demonstrate that thrombus tended to form on the interior side of the aorta arch and iliac branches, and cardiac function can affect blood flow field and affect thrombus formation, which is consistent with the four patients' post-operative imaging follow-up. We also found that RRT, OSI, TAWSS in thrombosis area are lower than whole average. In addition, we found that the thrombus formation has negative correlations with the maximum ventricular contractile force (r = -.281 ± .101) and positive correlations with the minimum ventricular contractile force (r = .238 ± .074), whereas the effect of heart rate (r = -.015 ± .121) on thrombus formation is not significant. Conclusion: In conclusion, changes in ventricular systolic function may alter the risk of thrombotic events after EVAR repair, which could provide insight into the selection of adjuvant therapy strategies for AAA patients with CHD.

Introduction: Aortic aneurysm is a life-threatening disease resulted from progressive dilatation of the aorta, which can be subdivided into thoracic and abdominal aortic aneurysms. Sustained subcutaneous angiotensin II infusion can induce aortic aneurysms in mice. However, the relevance of using angiotensin II induction model to study aneurysm disease and the degree of commonality between species remain elusive. Methods: We utilized scRNA-seq to infer aortic cell sub-structures and transcriptional profiles in clinical patient TAAs and AAAs, as well as mouse models of corresponding diseases (Ang II induction) and in healthy mouse aorta. Unbiased comparison between mice and humans explored the possible reasonability and utility of mouse Ang II-induced aortic aneurysm as a model for human aortic aneurysm diseases. Meanwhile, we performed comparative analysis of aortic aneurysms between TAA and AAA in both organisms. Results and Discussion: We demonstrated similarities and differences of changes in the components of human and mouse cell types, and our unbiased comparison between mouse and human identified well conserved subpopulations of SMCs and macrophages. Furthermore, the results of our comparative analyses suggested different biological functions and distinct potential pathogenic genes for thoracic and abdominal aortic aneurysms. MIF and SPP1 signaling networks participated in aortic aneurysm in both organisms. This study maps aortic aneurysm and offers opportunities for future researches to investigate the potential of subpopulations or marker genes as therapy targets.

Rupture risk estimation of abdominal aortic aneurysm (AAA) patients is currently based on the maximum diameter of the AAA. Mechanical properties that characterize the mechanical state of the vessel may serve as a better rupture risk predictor. Non-electrocardiogram-gated (non-ECG-gated) freehand 2D ultrasound imaging is a fast approach from which a reconstructed volumetric image of the aorta can be obtained. From this 3D image, the geometry, volume, and maximum diameter can be obtained. The distortion caused by the pulsatility of the vessel during the acquisition is usually neglected, while it could provide additional quantitative parameters of the vessel wall. In this study, a framework was established to semi-automatically segment probe tracked images of healthy aortas (N = 10) and AAAs (N = 16), after which patient-specific geometries of the vessel at end diastole (ED), end systole (ES), and at the mean arterial pressure (MAP) state were automatically assessed using heart frequency detection and envelope detection. After registration AAA geometries were compared to the gold standard computed tomography (CT). Local mechanical properties, i.e., compliance, distensibility and circumferential strain, were computed from the assessed ED and ES geometries for healthy aortas and AAAs, and by using measured brachial pulse pressure values. Globally, volume, compliance, and distensibility were computed. Geometries were in good agreement with CT geometries, with a median similarity index and interquartile range of 0.91 [0.90-0.92] and mean Hausdorff distance and interquartile range of 4.7 [3.9-5.6] mm. As expected, distensibility (Healthy aortas: 80 ± 15·10-3 kPa-1; AAAs: 29 ± 9.6·10-3 kPa-1) and circumferential strain (Healthy aortas: 0.25 ± 0.03; AAAs: 0.15 ± 0.03) were larger in healthy vessels compared to AAAs. Circumferential strain values were in accordance with literature. Global healthy aorta distensibility was significantly different from AAAs, as was demonstrated with a Wilcoxon test (p-value = 2·10-5). Improved image contrast and lateral resolution could help to further improve segmentation to improve mechanical characterization. The presented work has demonstrated how besides accurate geometrical assessment freehand 2D ultrasound imaging is a promising tool for additional mechanical property characterization of AAAs.

Abdominal aortic aneurysm (AAA) is a life-threatening disease and there is currently a lack of effective treatment to prevent it rupturing. ScRNA-seq studies of AAA are still lacking. In the study, we analyzed the published AAA scRNA-seq datasets from the mouse elastase-induced model, CaCl2 treatment model, Ang II-induced model and human by using bioinformatic approaches and in silico analysis. A total of 26 cell clusters were obtained and 11 cell types were identified from multiple mouse AAA models. Also, the proportion of Mφ/Mo increased in the AAA group and Mφ/Mo was divided into seven subtypes. There were significant differences in transcriptional regulation patterns of Mφ/Mo in different AAA models. The enrichment pathways of upregulated or downregulated genes from Mφ/Mo in the three mouse datasets were different. The actived regulons of Mφ/Mo had strong specificity and the repressed regulons showed high consistency. The co-upregulated genes as well as actived regulons and co-downregulated genes as well as repressed regulons were closely correlated and formed regulatory networks. Mφ/Mo from human AAA dataset was divided into five subtypes. The proportion of three macrophage subpopulations increased but the proportion of two monocyte subpopulations decreased. In the AAA group, the upregulated or downregulated genes of Mφ/Mo were enriched in different pathways. After further analyzing the genes in Mφ/Mo of both mouse and human scRNA-seq datasets, two genes were upregulated in the four datasets, IL-1B and THBS1. In conclusion, in silico analysis of scRNA-seq revealed that Mφ/Mo and their regulatory related genes as well as interaction networks played an important role in the pathogenesis of AAA.

Cumulative evidence has shown that mechanical and frictional forces exert distinct effects in the multi-cellular aortic layers and play a significant role in the development of abdominal aortic aneurysms (AAA). These mechanical cues collectively trigger signaling cascades relying on mechanosensory cellular hubs that regulate vascular remodeling programs leading to the exaggerated degradation of the extracellular matrix (ECM), culminating in lethal aortic rupture. In this review, we provide an update and summarize the current understanding of the mechanotransduction networks in different cell types during AAA development. We focus on different mechanosensors and stressors that accumulate in the AAA sac and the mechanotransduction cascades that contribute to inflammation, oxidative stress, remodeling, and ECM degradation. We provide perspectives on manipulating this mechano-machinery as a new direction for future research in AAA.

Aortic aneurysm (AA) is a vascular disorder characterized pathologically by inflammatory cell invasion and extracellular matrix (ECM) degradation. It is known that regulation of the balance between pro-inflammatory M1 macrophages (M1Ms) and anti-inflammatory M2 macrophages (M2Ms) plays a pivotal role in AA stabilization. We investigated the effects of M2M administration in an apolipoprotein E-deficient (apoE-/-) mouse model in which AA was induced by angiotensin II (ATII) infusion. Mice received intraperitoneal administration of 1 million M2Ms 4 weeks after ATII infusion. Compared with a control group that was administered saline, the M2M group exhibited reduced AA expansion; decreased expression levels of interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), and monocyte chemoattractant protein-1 (MCP-1); and a lower M1M/M2M ratio. Moreover, the M2M group exhibited upregulation of anti-inflammatory factors, including IL-4 and IL-10. PKH26-labeled M2Ms accounted for 6.5% of cells in the aneurysmal site and co-expressed CD206. Taken together, intraperitoneal administration of M2Ms inhibited AA expansion by reducing the inflammatory reaction via regulating the M1M/M2M ratio. This study shows that M2M administration might be useful for the treatment of AA.

Abdominal aortic aneurysm (AAA) is one of the leading causes of death worldwide. AAAs often remain asymptomatic until they are either close to rupturing or they cause pressure to the spine and/or other organs. Fast progression has been linked to future clinical outcomes. Therefore, a reliable and efficient system to quantify geometric properties and growth will enable better clinical prognoses for aneurysms. Different imaging systems can be used to locate and characterize an aneurysm; computed tomography (CT) is the modality of choice in many clinical centers to monitor later stages of the disease and plan surgical treatment. The lack of accurate and automated techniques to segment the outer wall and lumen of the aneurysm results in either simplified measurements that focus on few salient features or time-consuming segmentation affected by high inter- and intra-operator variability. To overcome these limitations, we propose a model for segmenting AAA tissues automatically by using a trained deep learning-based approach. The model is composed of three different steps starting with the extraction of the aorta and iliac arteries followed by the detection of the lumen and other AAA tissues. The results of the automated segmentation demonstrate very good agreement when compared to manual segmentation performed by an expert.

Injectable hydrogels with strong mechanical properties have significant potential for biomedical applications, including the development of electronic skin, intelligent medical robots, as well as tissue engineering. In this study, we report on an injectable hydrogel with notable tensile strength and adhesion properties, achieved through cross-linking thiol-terminated four-arm poly (ethylene glycol) using silver-doped nano-hydroxyapatite, modified with dopamine. Subsequently, the hydrogel was injected in vivo through the perivascular interstitial space of rats. The hydrogel wrapped around the damaged abdominal aortic adventitia, which greatly increases the stress strength of the arterial adventitia. We found that the hydrogel was characterized by excellent biocompatibility, and it induced little immune response over a span of 21 days post-implantation. This simple and minimally invasive vascular protection strategy appears promising for the treatment of vascular diseases, such as abdominal aortic aneurysm (AAA).