Normal Abdominal Aorta Research Articles

The correlation between the number of endothelial progenitor cells in the peripheral blood and abdominal aortic aneurysm.

This study was to investigate the correlation between the number of endothelial progenitor cells (EPCs) in peripheral blood and abdominal aortic aneurysm (AAA), and provide a potential biomarker for the diagnosis and treatment monitoring of AAA. Patients with AAA evaluated in the First Affiliated Hospital of Soochow University from June 2018 to October 2018 (n = 7) were included in this study. All patients were confirmed as AAA by vascular CTA with an increase of more than 50% of the abdominal aortic diameter. Patients (n = 7) with normal abdominal aorta diameter were included as control group with matching age, sex, blood pressure, and blood sugar concentration between experimental and control groups. Mononuclear cells were collected by density gradient centrifugation, stained by CD34-FITC and CD309-PE antibodies, and analyzed by flow cytometry. The number of EPCs in the peripheral blood of patients with AAA (0.874 ± 0.129‰) was significantly lower than that in the control group (1.420 ± 0.289‰) (P < .01). The number of EPCs may be used as a potential biomarker for the diagnosis and monitoring of AAA following treatment.

Influence of Age, Gender and BMI on Normal Abdominal Aorta Diameter taken on Abdominal Sonography in Healthy Asymptomatic Pakistani Population

Objective: To evaluate the abdominal aorta diameter in asymptomatic Pakistani population to determine the associations between age, gender and BMI and abdominal aortic diameter measured by ultrasonography. Study Design: Case series. Place and Duration of Study: Department of Radiology, Combined Military Hospital, Lahore, Pakistan, from Jun to Dec 2021. Methodology: A total of ninety-four healthy asymptomatic subjects of both genders, between 18-80 years of age, were enrolled for the study. Aortic diameters were measured (inner to inner method) using electronic calipers on static images. The Anteroposterior and Transverse (TR) diameters were measured at three levels: the first at the aortic hiatus, which was directly below the abdominal aortic commencement, the second at the suprarenal (mid-point), and the third at the aortic bifurcation (lower level). Results: Males had significantly larger (p-value&lt;0.001) anteroposterior and transverse abdominal aorta diameters than females, with abdominal aorta diameter values found to be significantly higher (p-value 0.001) in age group of greater than 40 years except anteroposterior distal abdominal aorta diameter. Similarly, a significant difference (p-value &lt;0.001) was noted in abdominal aorta diameter among patients with different BMI groups other than distal abdominal aorta diameter. Conclusion: Abdominal aorta diameters vary greatly depending on age, gender and BMI. Clinicians must know the usual diameter of the abdominal aorta in order to recognize an aneurysm at an early stage.

Comprehensive transcriptomic analysis unveils macrophage-associated genes for establishing an abdominal aortic aneurysm diagnostic model and molecular therapeutic framework

BackgroundAbdominal aortic aneurysm (AAA) is a highly lethal cardiovascular disease. The aim of this research is to identify new biomarkers and therapeutic targets for the treatment of such deadly diseases.MethodsSingle-sample gene set enrichment analysis (ssGSEA) and CIBERSORT algorithms were used to identify distinct immune cell infiltration types between AAA and normal abdominal aortas. Single-cell RNA sequencing data were used to analyse the hallmark genes of AAA-associated macrophage cell subsets. Six macrophage-related hub genes were identified through weighted gene co-expression network analysis (WGCNA) and validated for expression in clinical samples and AAA mouse models. We screened potential therapeutic drugs for AAA through online Connectivity Map databases (CMap). A network-based approach was used to explore the relationships between the candidate genes and transcription factors (TFs), lncRNAs, and miRNAs. Additionally, we also identified hub genes that can effectively identify AAA and atherosclerosis (AS) through a variety of machine learning algorithms.ResultsWe obtained six macrophage hub genes (IL-1B, CXCL1, SOCS3, SLC2A3, G0S2, and CCL3) that can effectively diagnose abdominal aortic aneurysm. The ROC curves and decision curve analysis (DCA) were combined to further confirm the good diagnostic efficacy of the hub genes. Further analysis revealed that the expression of the six hub genes mentioned above was significantly increased in AAA patients and mice. We also constructed TF regulatory networks and competing endogenous RNA networks (ceRNA) to reveal potential mechanisms of disease occurrence. We also obtained two key genes (ZNF652 and UBR5) through a variety of machine learning algorithms, which can effectively distinguish abdominal aortic aneurysm and atherosclerosis.ConclusionOur findings depict the molecular pharmaceutical network in AAA, providing new ideas for effective diagnosis and treatment of diseases.

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.

Reference for Normal Diameters of the Abdominal Aorta and Common Iliac Arteries in the Saudi Population.

The abdominal aorta is the largest artery in the abdomen. It then bifurcates giving the two common iliac arteries. Knowing the normal abdominal aorta diameter is a basis for diagnosing abdominal aortic aneurysms (AAAs) and subsequently developing an optimal management plan. In order to diagnose AAA, one must have a reference for the normal abdominal aortic diameter that represents the anatomical variation in the population being studied. The aim of this research is to establish normal abdominal aortic diameters in the Saudi population.

Influence of the flow field and vortex structure of patient-specific abdominal aortic aneurysm with intraluminal thrombus on the arterial wall

ABSTRACT In this study, numerical simulations and experiments were conducted on patient-specific normal abdominal aorta and abdominal aortic aneurysm (AAA) with intraluminal thrombus (ILT) models, which were reconstructed from computed tomography angiography (CTA) images published online. A scale-adaptive simulation (SAS) of the abdominal aortic aneurysm with a posterior eccentric thrombus was performed and the reliability of the numerical simulation was verified by 2D particle image velocimetry (PIV) experimental results. The distribution of wall shear stress (WSS), oscillatory shear index (OSI), and relative residence time (RRT) of the normal abdominal aorta and AAA were compared and discussed systematically according to the numerical simulation results under rest and exercise conditions. Numerical results indicated that ILT deposition positions were accompanied by low WSS, high OSI, and high RRT regions and were characterized by small vortex groups, which was due to the fragmentation of large vortex structures. The distribution law of the AAA wall parameters has an obvious correlation with the nearby vortex structure formation, development, fragmentation and dissipation. It was also found that high TAWSS, low OSI, and low RRT regions present in the middle and lower aneurysm walls under exercise condition reduce the risk of ILT formation and development.

Reference values of normal abdominal aortic areas in Chinese population measured by contrast-enhanced computed tomography.

ObjectiveTo generate reference values of the normal areas of the abdominal aorta at various levels among Chinese people and to explore the factors that may promote the expansion of the abdominal aorta.MethodsThe areas of normal abdominal aortas were gauged at various levels based on inner-to-inner measurements in 1,066 Chinese adult patients (>18 years) without the abdominal aortic disease. The areas of subphrenic abdominal, suprarenal abdominal, infrarenal abdominal, and distal abdominal aortas were measured. The demographic and clinical characteristics were collected into a specifically designed electronic database. Multivariable linear regression was used to analyze the potential risk factors promoting the expansion of the abdominal aorta.ResultsIn males, the median areas of the subphrenic abdominal aorta, suprarenal abdominal aorta, infrarenal abdominal aorta, and distal abdominal aorta were 412.1, 308.0, 242.2, and 202.2 mm2, respectively. In females, the median areas of the subphrenic abdominal aorta, suprarenal abdominal aorta, infrarenal abdominal aorta, and distal abdominal aorta were 327.7, 243.4, 185.4, and 159.6 mm2, respectively. The areas of the abdominal aorta at different levels were larger in males than in females and increased with age. Multiple linear stepwise regression analysis showed that the subphrenic abdominal aortic area was significantly related to age (β = 0.544, p < 0.001), sex (β = 0.359, p < 0.001), and hypertension (β = 0.107, p < 0.001). Suprarenal abdominal aortic area was related to age (β = 0.398, p < 0.001), sex (β = 0.383, p < 0.001), history of smoking (β = 0.074, p = 0.005), and hypertension (β = 0.111, p < 0.001). The infrarenal abdominal aortic area was correlated with age (β = 0.420, p < 0.001), sex (β = 0.407, p < 0.001), and history of smoking (β = 0.055, p = 0.036). The distal abdominal aortic area was correlated with age (β = 0.463, p < 0.001), sex (β = 0.253, p < 0.001), and hypertension (β = 0.073, p = 0.013).ConclusionThe abdominal aortic areas at different levels were larger in males than in females. Aging, hypertension, and smoking prompt the expansion of abdominal aorta.

Bioinformatic analyses of the role of m6A RNA methylation regulators in abdominal aortic aneurysm.

BackgroundN6-methyladenosine (m6A) is found in almost all nuclear RNAs of eukaryotes, playing an important and diverse role in many biological processes. Nonetheless, the roles of m6A regulators in abdominal aortic aneurysm (AAA) unknown. Therefore, there is a pressing need to identify m6A RNA methylation regulators in the diagnosis of AAA, determination of individualized risk, discovery of therapeutic targets, and improve understanding of pathogenesis.MethodsThe GSE98278 dataset were obtained from the Gene Expression Omnibus (GEO) database to perform differential analysis of m6A-related regulators between elective stable abdominal aortic aneurysms (eAAA) and abdominal aortic aneurysm ruptured (rAAA). The random forest model was used to screen candidate m6A regulators to predict the risk of rAAA. The single sample gene set enrichment analysis (ssGSEA) method was then used to evaluate the abundance of 23 immune cells in AAA. The m6A RNA Methylation Quantification Kit was used to measure the total m6A levels of AAA and normal abdominal aorta. The terminal deoxynucleotidyl transferase mediated dUTP Nick-End Labeling (TUNEL) apoptosis assay kit was used to detect the human aortic smooth muscle cells (HASMCs) apoptotic after RBM15 knockdown. Mechanically, RBM15 knockdown was found to reduce the expression of CASP3 in an m6A-dependent manner by Western blotting, RNA immunoprecipitation (RIP), and methylated RNA immunoprecipitation-quantitative polymerase chain reaction (MeRIP-RT-PCR).ResultsRBM15, WTAP, ALKBH5, and IGFBP3 were highly expressed in rAAA. In contrast, RBM15B showed opposite results (P<0.05). The high m6A level in the rAAA compared with eAAA and normal abdominal aorta (P<0.05). The random forest model was used to screen 5 candidate m6A regulators to predict the risk of rAAA. Expression of the 5 m6A methylation regulators was validated in AAA samples (P<0.05). RBM15 knockdown inhibited the apoptosis of HASMCs. RBM15 knockdown reduced the expression of CASP3 in an m6A-dependent manner. A strong correlation between the five m6A methylation regulators and immune cell infiltration was identified.ConclusionsIn summary, m6A regulators play nonnegligible roles in the occurrence of rAAA. Our investigation of m6A patterns may be able to guide future immunotherapy strategies for AAA.

EGR1 and KLF4 as Diagnostic Markers for Abdominal Aortic Aneurysm and Associated With Immune Infiltration.

BackgroundFormation and rupture of abdominal aortic aneurysm (AAA) is fatal, and the pathological processes and molecular mechanisms underlying its formation and development are unclear. Perivascular adipose tissue (PVAT) has attracted extensive attention as a newly defined secretory organ, and we aim to explore the potential association between PVAT and AAA.MethodsWe analyzed gene expression and clinical data of 30 PVAT around AAA and 30 PVAT around normal abdominal aorta (NAA). The diagnostic markers and immune cell infiltration of PVAT were further investigated by WGCNA, CIBERSORT, PPI, and multiple machine learning algorisms (including LASSO, RF, and SVM). Subsequently, eight-week-old C57BL/6 male mice (n = 10) were used to construct AAA models, and aorta samples were collected for molecular validation. Meanwhile, fifty-five peripheral venous blood samples from patients (AAA vs. normal: 40:15) in our hospital were used as an inhouse cohort to validate the diagnostic markers by qRT-PCR. The diagnostic efficacy of biomarkers was assessed by receiver operating characteristic (ROC) curve, area under the ROC (AUC), and concordance index (C-index).ResultsA total of 75 genes in the Grey60 module were identified by WGCNA. To select the genes most associated with PVAT in the grey60 module, three algorithms (including LASSO, RF, and SVM) and PPI were applied. EGR1 and KLF4 were identified as diagnostic markers of PVAT, with high accurate AUCs of 0.916, 0.926, and 0.948 (combined two markers). Additionally, the two biomarkers also displayed accurate diagnostic efficacy in the mice and inhouse cohorts, with AUCs and C-indexes all >0.8. Compared with the NAA group, PVAT around AAA was more abundant in multiple immune cell infiltration. Ultimately, the immune-related analysis revealed that EGR1 and KLF4 were associated with mast cells, T cells, and plasma cells.ConclusionEGR1 and KLF4 were diagnostic markers of PVAT around AAA and associated with multiple immune cells.

Comparative Study of Aortic Wall Stress According to Geometric Parameters in Abdominal Aortic Aneurysms

In abdominal aortic aneurysm (AAA), the rupture of the aortic tissue is directly related to wall stress. Thus, the investigation of maximum wall stress is a necessary procedure to predict the aortic rupture in AAA. In this study, computational simulations were performed to investigate the correlation between peak wall stress (PWS) and AAA geometry. The Holzapfel model and various orientations of the collagen fibers and thicknesses of the layers of the aorta were employed in the simulation. The material constants used in the Holzapfel model were estimated from the examination and analysis of the biaxial tensile test results of the normal abdominal aorta and AAA. The aneurysm diameter, height, neck angle, and iliac angle were selected as geometric factors affecting the AAA rupture. In addition, a simulation scenario was conceived and created based on the measurement results using the computed tomography data of patients with AAA. Accordingly, the correlation between the PWS and AAA geometry was estimated.

A novel role for local immune suppression in chronic q fever infected abdominal aortic aneurysms?

Abstract Background Chronic Q fever (QCF) is the persistence of C. Burnettii after an acute infection. Atheromas in the abdominal aorta are a preferential location of this bacterial persistence and may result in accelerated abdominal aorta aneurysm (AAA) formation or even rupture. CQF is characterized by a poor response to antibiotic therapy with high mortality. The localization of the bacteria in the acidic lysosomes is thought to be the main cause of poor antibiotic efficacy. Purpose A potent immune system is mandatory for successful antibiotic therapy. PBMC simulation assays have shown potent immune activation on stimulation with C. Burnettii. Here we assess whether this holds true in situ by combining 3 six-marker panels with phenotypical markers describing the adaptive and innate immune system and looking at key check-points in immune regulation. Methods (Tissue) PCR-positive CQF infected AAAs (n=10) are compared to atherosclerotic AAAs (n=13) and normal abdominal aortas from kidney transplant donors (n=3). We combine DAPI and elastin autofluorescence with 3 distinct panels of 6 markers in an 8-color IHC technique (Vectra 3, Perkin Elmer, MA) to describe the local immune landscape. The panels focus on 1) adaptive immune response, 2) innate immune response and 3) checkpoint inhibitors. Cells were phenotyped and quantified using an automated quantitative analysis method. Results In contrast to normal abdominal aortas, both atherosclerotic AAAs and CQF AAAs show impressive lymphocyte recruitment and proliferation with the formulation of very large tertiary lymphoid structures. CQF AAAs show a 2-fold increase in regulatory T cell numbers compared to atherosclerotic AAAs. These regulatory cells are both surrounding germinal centers and are seen throughout the tissue. Additionally, CQF AAAs show more positive cells and a higher expression of PD-L1, which is a key immunosuppressive mediator. Conclusion The immune landscape within the aortic wall shows far greater immune suppression than previously found in in vitro and peripheral blood studies. We show that CQF infections are associated with severely increased numbers of regulatory T cells, even compared to the low-grade and chronic inflammation present in atherosclerosis. Subsequently, a look at the immune checkpoint PD-L1 shows an increased expression in CQF aortas, elucidating a possible underlying mechanism and treatment target. Figure 1. Representative microscopy images of normal (left) atherosclerotic AAA (middle) and CQF AAA (right), full thickness overview (top row) and magnified region off interest (bottom row). Vast increase in regulatory T cells (FoxP3+), recognisable by the yellow nucleus, surrounding germinal centres in only the CQF aorta. Furthermore, DAPI in blue, B cells in green, helper T cells in red, cytotoxic T cells in cyan, classic DC type 2 in magenta. Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): ERC starting grant (ERC-2014-StG-336454-CoNQUeST); TTW-NWO open technology grant (STW-14716)

MiR-146a regulates inflammation and development in patients with abdominal aortic aneurysms by targeting CARD10.

We present the expression of miR-146a in abdominal aortic aneurysms (AAA) patients, and its mechanism for regulating inflammation and development in AAA patients. The expression of miR-146a in serum, PBMC, and abdominal aorta tissues was measured in AAA patients. We found that level of miR-146a in the serum and its expression in AAA tissues were significantly higher than that in healthy people or normal abdominal aorta tissues. Pearson's method analysis showed that miRNA-146a in the serum of AAA patients was negatively correlated with serum TNF-α, IFN-γ and CRP, and was positively correlated with serum IL-10. The luciferase reporter gene system confirmed that miR-146a targeted inhibition of CARD10 expression in THP-1 and human umbilical vein endothelial cells (HUVECs), and miR-146a was negatively correlated with the expression of CARD10 in the tissues/PBMC of AAA patients. In PBMC of healthy people, over-expression of miR-146a by transferring miR-146a-mimic could increase the expression of SIRT1 but decreased the expression of p65 and the level of TNF-α secretion. Moreover, HUVECs cellular activity change by TNF-α in a dose-dependent manner. These results suggested that miR-146a suppressed the inflammation of peripheral blood in AAA patients by targeting CARD10, and miR-146a blocked the progression of AAA through CARD10/SIRT1/p65 pathway.

Elastase Fibrinolysis as a Marker of Presence, Size and Mechanical Stress of Abdominal Aortic Aneurysms and its Intraluminal Thrombi

Introduction - Most clinically relevant abdominal aortic aneurysms (AAA) contain an intraluminal thrombus (ILT) 1. The ILT entraps neutrophils, which secrete elastase with fibrinolytic activity, the process of which yields specific ‘neutrophil elastase-derived cross-linked fibrin degradation products’ (E-XDP) 2. Our hypothesis was that circulating E-XDP could reveal the presence, size and mechanical stress of AAAs and its ILTs. Methods - E-XDP was quantified by ELISA in plasma from 42 male patients with AAA and 42 male controls. The ILT volumes of the AAAs and any coexisting aneurysms could be measured in 32 patients. Finite element analysis was performed in the same 32 patients to estimate mechanical stress of the ILT. Local expression of E-XDP, neutrofil elastase and neutrophil marker CD66acd was studied by immunohistochemistry (IHC) in tissue from AAA and normal abdominal aorta. Wilcoxon rank sum test, receiver operating characteristic analysis, multivariate linear regression and Spearman’s rank were used to test univariate hypotheses, binary classification, correlations, and multivariate associations, respectively. Results - E-XDP levels were elevated in patients with AAA compared with controls (p = 6.9e-14), predicted AAA with 98% sensitivity and 88% specificity and correlated with the AAA diameter (r = 0.58, p = 5.3e-05). The association between AAA and increased E-XDP was independent of smoking, comorbidities and prescription drugs (p = 2.6e-06). Levels of E-XDP in patients with only a thin or macroscopically non-existent ILT were lower than those of patients with a large ILT, but remained significantly higher than in controls (p = 0.0026). Concentration of E-XDP correlated with volume of the ILTs in the AAAs (r = 0.75, p = 1.0e-06) and mean ILT stress (r = 0.42, p = 0.017), and was independently raised if coexisting aneurysms existed (p = 0.015). IHC revealed E-XDP expression in the ILT, which was spatially related to luminal neutrophil elastase and neutrophils. Conclusion - Circulating E-XDP is a novel marker of AAA and coexisting aneurysms, and correlates with AAA and ILT volume as well as with the mechanical stress of the ILT.

Silencing of NONO inhibits abdominal aortic aneurysm in apolipoprotein E‐knockout mice via collagen deposition and inflammatory inhibition

The role of Non‐POU‐domain‐containing octamer‐binding protein (NONO) in the formation and development of angiotensin II (Ang II)‐induced abdominal aortic aneurysm (AAA) in apolipoprotein E‐knockout (ApoE−/−) mice is still unknown. In Part I, the protein level of NONO was suggestively greater in the AAA tissues compare to that in the normal abdominal aortas. In Part II, 20 ApoE−/− male mice were used to examine the transfection efficiency of lentivirus by detecting GFP fluorescence. In Part III, mice were arbitrarily separated into two groups: one was the control group without Ang II infusion, and another was the Ang II group. Mice treated with Ang II were further randomly divided into three groups to receive the same volume of physiological saline (NT group), sh‐negative control lentivirus (sh‐NC group) and si‐NONO lentivirus (sh‐NONO group). NONO silencing suggestively reduced the occurrence of AAA and abdominal aortic diameter. Compare to the NT group, NONO silencing markedly augmented the content of collagen and vascular smooth muscle cells but reduced macrophage infiltration in AAA. In addition, knockdown of NONO also increased the expression of prolyl‐4‐hydroxylase α1, whereas also decreased the levels of collagen degradation and pro‐inflammatory cytokines in AAA. We detected the interface of NONO and NF‐κB p65, and found that NONO silencing inhibited both the nuclear translocation and the phosphorylation levels of NF‐κB p65. Silencing of NONO prevented Ang II‐influenced AAA in ApoE−/− mice through increasing collagen deposition and inhibiting inflammation. The mechanism may be that silencing of NONO decreases the nuclear translocation and phosphorylation of NF‐κB.

Normal abdominal aorta diameter on abdominal sonography in healthy asymptomatic adults: impact of age and gender

ABSTRACTThe study aims to establish the normal criterion of abdominal aortic diameters measured on abdominal sonography based on gender and age, and to study the variation in aortic diameters with ...

Abstract 261: Proteomic Analysis of Infrarenal and Suprarenal Aorta in a Kawasaki Disease Vasculitis Murine Model Associated with Infrarenal Abdominal Aorta Dilatation and Aneurysms

Background: Kawasaki Disease (KD) is a childhood vasculitis that leads to coronary artery aneurysms and is the leading cause of acquired heart diseases among children in the USA. We have reported that the L actobacillus casei - c ell w all e xtract (LCWE)-induced murine model of KD vasculitis and coronary arteritis also induces abdominal aorta dilatation and aneurysms (AAA) that involve exclusively the infrarenal (IR) region of the abdominal aorta (AA) without affecting the suprarenal (SR)-AA. AAA predisposes tissue to dissection and rupture, and is potentially life-threatening in humans. While differences in blood flow, tissue elasticity and different embryonic origin of vascular cells have been proposed among possible explanations for the preferential location of AAA disease in the IR aorta, the mechanism(s) for this is still not known. Objective: To determine and compare the proteomes of the IR vs SR aorta regions in naïve mice and during KD vasculitis induced AAA development. Methods and Results: By using data-independent mass-spectrometry, we compared the proteomes of the IR and SR aortas isolated from control naïve mice and LCWE-injected KD vasculitis mice. Proteomic analysis revealed significant differential expression of 340 proteins between the IR aorta from control vs KD mice, and 407 differentially expressed proteins between the IR and SR aorta regions of KD mice. The differentially expressed proteins include those involved in cytoskeletal reorganization, cell motility and adhesion as well as acute phase and oxidative stress responses. Ingenuity Pathway Analysis reveals the activation of key regulators of innate immune responses as well as the ER Stress response. TGF-β1, IL-6, and IL-1β are regulators of several protein that were activated in the IR aortic tissues. Conclusion: Proteomic differences exist between normal AA vs AAA and in IR vs SR aorta regions isolated from mice developing AAA. We show that a broad inflammatory response is generated in the aneurysm which maybe critical for the development and progression of the AAA and may provide possible novel therapeutic targets. (Supported by AHA 17SDG33671141 to MNR and NIH R01AI07272607 to MA).

Normal abdominal aorta diameter in infants, children and adolescents

The normal limits of arterial diameters must be known to diagnose pathologies such as dilatation, stenosis and hypoplasia. Thoracic aorta diameter in childhood has been measured in previous studies, but the number of studies in which normal aortic diameter is determined is very small. The aim of this study was therefore to determine the normal standard diameter of the aorta and iliac arteries in children according to gender and level. Pediatric abdominal computed tomography carried out for various reasons was retrospectively re-evaluated between January 2016 and February 2017. Patients were classified according to age into six groups. Vessel diameter, age, gender and vertebra diameter were evaluated. Mean proximal aorta diameter was 8.84mm for 12-36months, 10.02mm for 37-84months, 12.32mm for 85-132months, 14.45mm for 133-180months, and 16.51mm for 181-204months. Mean distal aorta diameter was 6.67mm for 12-36months, 8.07mm for 37-84months, 10.79mm for 85-132months, 12.14mm for 133-180months, and 14.01mm for 181-204months. The lumen diameter of the abdominal aorta, both proximally and distally, correlated linearly with age as an independent predictor. Similarly, the lumen diameter of the right and left common iliac artery correlated linearly with age as an independent predictor. There was no statistically significant difference in vascular diameter according to gender in any age groups. Optimal evaluation of aortic diameter is possible on computed tomography. Measurement outside the normal range is a sign of aneurysm or hypoplasia.

A "Sound" Approach.

A "Sound" Approach.

Synergy between shear-induced migration and secondary flows on red blood cells transport in arteries: considerations on oxygen transport.

Shear-induced migration of red blood cells (RBCs) is a well-known phenomenon characterizing blood flow in the small vessels (micrometre to millimetre size) of the cardiovascular system. In large vessels, like the abdominal aorta and the carotid artery (millimetre to centimetre size), the extent of this migration and its interaction with secondary flows has not been fully elucidated. RBC migration exerts its influence primarily on platelet concentration, oxygen transport and oxygen availability at the luminal surface, which could influence vessel wall disease processes in and adjacent to the intima. Phillips' shear-induced particle migration model, coupled to the Quemada viscosity model, was employed to simulate the macroscopic behaviour of RBCs in four patient-specific geometries: a normal abdominal aorta, an abdominal aortic aneurysm (AAA), a normal carotid bifurcation and a stenotic carotid bifurcation. Simulations show a migration of RBCs from the near-wall region with a lowering of wall haematocrit (volume fraction of RBCs) on the posterior side of the normal aorta and on the lateral-external side of the iliac arteries. A marked migration is observed on the outer wall of the carotid sinus, along the common carotid artery and in the carotid stenosis. No significant migration is observed in the AAA. The spatial and temporal patterns of wall haematocrit are correlated with the near-wall shear layer and with the secondary flows induced by the vessel curvature. In particular, secondary flows accentuate the initial lowering in RBC near-wall concentration by convecting RBCs from the inner curvature side to the outer curvature side. The results reinforce data in literature showing a decrease in oxygen partial pressure on the inner curvature wall of the carotid sinus induced by the presence of secondary flows. The lowering of wall haematocrit is postulated to induce a decrease in oxygen availability at the luminal surface through a diminished concentration of oxyhaemoglobin, hence contributing, with the reported lowered oxygen partial pressure, to local hypoxia.

Abstract 203: Smooth Muscle Cells from Abdominal Aortic Aneurysms are Unique and Can Independently and Synergistically Degrade Insoluble Elastin

Background The purpose of this study was to further elucidate the role of the vascular smooth muscle cell (SMC) in abdominal aortic aneurysm (AAA) disease. We hypothesized that that AAA-SMC are unique and actively participate in the process of degrading the aortic matrix. Methods and Results Whole-genome expression profiles of SMC from AAA, normal abdominal aorta (NAA) and carotid endarterectomy (CEA) were compared. We quantified elastolytic activity by culturing SMC in [3H]elastin-coated plates and measuring solubilized tritium in the media after 7 days. MMP-2 and MMP-9 production was assessed using real-time PCR, zymography and western blotting. Each SMC type exhibited a unique gene expression pattern. AAA-SMC had greater elastolytic activity than NAA (+68%, p&lt;0.001) and CEA-SMC (+45%, p&lt;0.001). Zymography showed an increase of active-MMP-2 (62kD) in media from AAA-SMC. AAA-SMC demonstrated 2-fold greater expression of MMP-2 mRNA (p&lt;0.05) and 7.3-fold greater MMP-9 expression (p&lt;0.01) than NAA-SMC. Culture with U937 monocytes caused a synergistic increase of elastolysis by AAA-SMC (41%, p&lt;0.001) but not NAA or CEA (p=0.99). Co-culture with U937 caused a large increase in MMP-9 mRNA in AAA and NAA-SMC (p&lt;0.001). MMP-2 mRNA expression was not affected. Western blots of culture media showed a 4-fold increase of MMP-9 (92kD) protein in AAA-SMC/U937 compared to NAA-SMC/U937 (p&lt;0.001) and a large increase in active-MMP2 (62kD) which was less apparent in NAA/U937 media (p&lt;0.01). Conclusions AAA-SMC have a unique gene expression profile and a pro-elastolytic phenotype that is augmented by macrophages. This may occur via a failure of post-transcriptional control of MMP-9 synthesis.