Suprarenal Aorta Research Articles

Feasibility of Assessing Inflammation in Asymptomatic Abdominal Aortic Aneurysms With Integrated 18F-Fluorodeoxyglucose Positron Emission Tomography/Magnetic Resonance Imaging

This study aimed to evaluate the feasibility of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) combined with contrast enhanced magnetic resonance imaging (MRI) to identify inflammation in asymptomatic abdominal aortic aneurysms (AAA). FDG PET/MRI was performed on 15 patients with asymptomatic infrarenal AAAs >45mm diameter. Prevalence of FDG uptake and MRI findings of inflammatory changes (oedema, wall thickening, and late gadolinium enhancement [LGE]) in the aortic wall were investigated at three levels: suprarenal aorta; non-aneurysmal aortic neck; and AAA. The median diameter of the AAAs was 54mm (range 47-65mm) and the median expansion rate in the last 12 months was 3mm (range 1-13mm). The standard uptake value (SUV) of FDG in the aneurysmal wall (SUVmax 2.5) was higher than the blood pool (SUVmax 1.0; p<.001). The maximum target to background ratio was higher in the suprarenal aorta (mean±SD; 3.1±0.6) and aortic neck (2.7±0.5) than in the aneurysmal aorta (2.5±0.5; p<.001). Thirty-six FDG hotspots were observed in the aneurysmal wall of 13 patients. Wall thickening and LGE were identified in eight patients. The number of FDG hotspots correlated with recent AAA growth (r=0.62, p=.01). The recent aneurysm expansion rate was higher in aneurysms with LGE than in those without (7mm vs. 2mm; p=.03). MRI inflammatory changes were observed in nine of 36 hot spots (25%) and in three of 13 patients with focal FDG uptake. Fully integrated FDG PET/MRI can be used to study inflammation in asymptomatic AAAs. Heterogenous uptake of FDG in the aneurysmal wall indicates increased glucose metabolism, suggesting an ongoing inflammation. However, these FDG hotspots rarely correspond to MRI findings of inflammation, raising the question of which type of cellular activity is present in these areas. The presence of LGE and FDG hotspots both correlated to recent aneurysm growth, and their usefulness as clinical markers of aneurysm growth warrant additional investigation.

FJVIS 17. Quantification of Suprarenal Aortic Neck Dilation After Fenestrated Endovascular Aneurysm Repair

Suprarenal aortic neck dilation (AND) after fenestrated endovascular aneurysm repair (FEVAR) has not yet been characterized. The aim of this study was to measure diameter changes in the juxtavisceral aorta after FEVAR. This is a single-center retrospective review involving patients with pararenal or juxtarenal aneurysms treated with Cook ZFEN devices (Cook, Bloomington, Ind). Patients with at least 1 year of radiologic follow-up were included. Aortic diameter, defined as the average outer-to-outer diameter on three-dimensional centerline imaging, was measured at seven locations along the length of the ZFEN device from the proximal fixation struts to the bottom of the second seal stent (Fig, left). The first postoperative computed tomography scan (≤1 month) served as a baseline with which subsequent measurements at annual intervals were compared. A total of 43 patients who underwent FEVAR met inclusion criteria, with a total of 119 target vessels (83 renal stents, 41 superior mesenteric artery scallops or large fenestrations). Median follow-up time was 30.3 months. AND at latest follow-up was found to occur at all measured locations from the top of the fixation struts (1.9 ± 2.4 mm; P < .001) to the bottom of the first seal stent (3.4 ± 3.3 mm; P < .001). AND was most pronounced in the middle of the first seal stent, with mean AND of 3.6 ± 3.2 mm (Fig). At this location, aortic diameter was found to increase at each interval compared with the baseline scan (mean, 1.4 mm/y). Aortic diameter did not significantly change along the second seal stent (−1.8 to +1.3 mm; P = .08-.1). AND ≥3 mm at any location was found to occur in 32 (74.4%) patients. Increasing device oversizing relative to the native visceral aorta was the strongest predictor of AND (0.34 mm per 10% increase in oversizing; P = .007), whereas increasing length of the seal zone was protective of AND (−1.97 mm per 10-mm increase in seal length; P = .023). Seal lengths ≥3 cm were associated with less AND compared with <3 cm (2.6 vs 4.9 mm; P = .022). However, type IA endoleak in this cohort was rare (n = 1). Dilation of the suprarenal aorta is a common and benign finding in midterm follow-up after FEVAR. Aggressive device oversizing is predictive of dilation, whereas longer seal lengths are associated with less dilation along the suprarenal seal zone.

Fenestrated Endovascular Aneurysm Repair versus Snorkel Endovascular Aneurysm Repair: Competing yet Complementary Strategies.

Juxtarenal/pararenal aortic aneurysms and type IV thoracoabdominal aneurysms pose particular technical challenges for endovascular repair as they involve the visceral segment in addition to insufficient infrarenal neck for the use of standard endovascular aneurysm repair (EVAR) devices. To overcome these challenges, complex EVAR techniques have been developed to extend the proximal landing zone cephalad with maintaining perfusion to vital aortic branches, thereby broadening the applicability of endografting from the infrarenal to the suprarenal aorta. Complex EVAR can be divided into two broad categories: fenestrated endovascular aneurysm repair (FEVAR) and snorkel EVAR. FEVAR is a valid procedure with the standardized procedure, although it remains as a relatively complex procedure with a learning curve. Given time constraints for the custom fenestrated graft, snorkel EVAR may be an alternative for complex repairs in symptomatic or ruptured patients for whom custom-made endografts may not be immediately available. This article discusses these two most commonly used complex EVAR strategies.

Progenitor/Stem Cell Delivery by Suprarenal Aorta Route in Acute Kidney Injury

Progenitor/stem cell-based kidney regenerative strategies are a key step towards the development of novel therapeutic regimens for kidney disease treatment. However, the route of cell delivery, e.g., intravenous, intra-arterial, or intra-parenchymal, may affect the efficiency for kidney repair in different models of acute and chronic injury. Here, we describe a protocol of intra-aorta progenitor/stem cell injection in rats following either acute ischemia-reperfusion injury or acute proteinuria induced by puromycin aminonucleoside (PAN) – the experimental prototype of human minimal change disease and early stages of focal and segmental glomerulosclerosis. Vascular clips were applied across both renal pedicles for 35 min, or a single dose of PAN was injected via intra-peritoneal route, respectively. Subsequently, 2 x 106 stem cells [green fluorescent protein (GFP)-labeled c-Kit+ progenitor/stem cells or GFP-mesenchymal stem cells] or saline were injected into the suprarenal aorta, above the renal arteries, after application of a vascular clip to the abdominal aorta below the renal arteries. This approach contributed to engraftment rates of ∼10% at day 8 post ischemia-reperfusion injury, when c-Kit+ progenitor/stem cells were injected, which accelerated kidney recovery. Similar rates of engraftment were found after PAN-induced podocyte damage at day 21. With practice and gentle surgical technique, 100% of the rats could be injected successfully, and, in the week following injection, ∼ 85% of the injected rats will recover completely. Given the similarities in mammals, much of the data obtained from intra-arterial delivery of progenitor/stem cells in rodents can be tested in translational research and clinical trials with endovascular catheters in humans.

Juxtarenal Aortic Aneurysm: Are We Ready for a Randomised Trial on Open versus Endovascular Repair?

In the last two decades, advances in endovascular aneurysm repair (EVAR) technology have led to the introduction of fenestrated (fEVAR) and branched (bEVAR) stent grafts for the treatment of juxta- and suprarenal abdominal aortic aneurysms (JRAAAs and SRAAAs), extending the proximal sealing zone from the infrarenal to the suprarenal aorta and expanding the EVAR indications to complex abdominal aortic aneurysms (AAAs).

Suprarenal Aortic Remodeling after Endovascular Aortic Aneurysm Repair among Three Endografts with Different Types of Proximal Fixation System

Remodeling of suprarenal aorta after endovascular aortic aneurysm repair (EVAR) in relation to different endograft designs has not been thoroughly investigated. The aim of this study is to assess the anatomical configuration of the suprarenal aorta after using endografts with different proximal fixation during the first post-EVAR year. A retrospective study including EVAR patients using 3 types of endografts with different proximal fixation systems according to Instructions for Use was undertaken (50: Ovation, Endologix, Irvin, CA; 25: Endurant IIs, Medtronic, Santa Rosa, CA; 25: Excluder C3, W. L. Gore & Associates, Flagstaff, AZ). Comorbidities were recorded. Anatomic variables of the supra-aortic anatomy, abdominal aortic aneurysm (AAA) maximum diameter, and neck angulation were analyzed. Computed tomography angiography was obtained preoperatively at 1 and 12months post-EVAR, while a duplex scan was undertaken at 6months. Comorbidities were not different across the 3 groups. Presence and amount of neck calcification (P=0.139) and thrombus (P=0.116) was similar among groups. Maximum aortic diameter showed significant reduction from preoperative measurements to 12-month postoperative ones, for all groups. (Ovation: 56.5 to 53mm, P<0.001; Endurant: 57 to 51mm, P<0.001; Excluder: 55 to 50mm, P<0.001). Suprarenal angulation was decreased significantly in the Ovation (P<0.001) and Excluder groups (P=0.05), while the infrarenal angulation was decreased in all groups. Among endografts, the decrease in AAA maximum diameter was similar (P=0.99), while the suprarenal aortic diameter was significantly increased in Ovation patients in comparison to the other 2 endografts at the level of 5mm (P=0.02) and 25mm (P=0.01). Suprarenal angulation reduction was similar (P=0.7), while infrarenal angulation was significantly more decreased in Ovation endograft than the other 2 systems (P<0.001). Proximal endograft configuration appears to have different impact on supra-aortic anatomy. Longer follow-up is needed to clarify future remodeling and clinical impact of these observations.

SGLT-2 (Sodium-Glucose Cotransporter 2) Inhibition Reduces Ang II (Angiotensin II)-Induced Dissecting Abdominal Aortic Aneurysm in ApoE (Apolipoprotein E) Knockout Mice.

Abdominal aortic aneurysm (AAA) is a pathological condition of permanent vessel dilatation that predisposes to the potentially fatal consequence of aortic rupture. SGLT-2 (sodium-glucose cotransporter 2) inhibitors have emerged as powerful pharmacological tools for type 2 diabetes mellitus treatment. Beyond their glucose-lowering effects, recent studies have shown that SGLT-2 inhibitors reduce cardiovascular events and have beneficial effects on several vascular diseases such as atherosclerosis; however, the potential effects of SGLT-2 inhibition on AAA remain unknown. This study evaluates the effect of oral chronic treatment with empagliflozin-an SGLT-2 inhibitor-on dissecting AAA induced by Ang II (angiotensin II) infusion in apoE (apolipoprotein E)-/- mice. Approach and Results: Empagliflozin treatment significantly reduced the Ang II-induced increase in maximal suprarenal aortic diameter in apoE-/- mice independently of blood pressure effects. Immunohistochemistry analysis revealed that empagliflozin diminished Ang II-induced elastin degradation, neovessel formation, and macrophage infiltration at the AAA lesion. Furthermore, Ang II infusion resulted in a marked increase in the expression of chemokines (CCL-2 [chemokine (C-C motif) ligand 2] and CCL-5 [chemokine (C-C motif) ligand 5]), VEGF (vascular endothelial growth factor), and MMP (matrix metalloproteinase)-2 and MMP-9 in suprarenal aortic walls of apoE-/- mice, and all were reduced by empagliflozin cotreatment. Western blot analysis revealed that p38 MAPK (p38 mitogen-activated protein kinase) and NF-κB (nuclear factor-κB) activation was also reduced in the suprarenal aortas of apoE-/- mice cotreated with empagliflozin. Finally, in vitro studies in human aortic endothelial cells and macrophages showed that empagliflozin inhibited leukocyte-endothelial cell interactions and release of proinflammatory chemokines. Pharmacological inhibition of SGLT-2 by empagliflozin inhibits AAA formation. SGLT-2 inhibition might represent a novel promising therapeutic strategy to prevent AAA progression.

Co-localization of microstructural damage and excessive mechanical strain at aortic branches in angiotensin-II-infused mice.

Animal models of aortic aneurysm and dissection can enhance our limited understanding of the etiology of these lethal conditions particularly because early-stage longitudinal data are scant in humans. Yet, the pathogenesis of often-studied mouse models and the potential contribution of aortic biomechanics therein remain elusive. In this work, we combined micro-CT and synchrotron-based imaging with computational biomechanics to estimate in vivo aortic strains in the abdominal aorta of angiotensin-II-infused ApoE-deficient mice, which were compared with mouse-specific aortic microstructural damage inferred from histopathology. Targeted histology showed that the 3D distribution of micro-CT contrast agent that had been injected in vivo co-localized with precursor vascular damage in the aortic wall at 3days of hypertension, with damage predominantly near the ostia of the celiac and superior mesenteric arteries. Computations similarly revealed higher mechanical strain in branching relative to non-branching regions, thus resulting in a positive correlation between high strain and vascular damage in branching segments that included the celiac, superior mesenteric, and right renal arteries. These results suggest a mechanically driven initiation of damage at these locations, which was supported by 3D synchrotron imaging of load-induced ex vivo delaminations of angiotensin-II-infused suprarenal abdominal aortas. That is, the major intramural delamination plane in the ex vivo tested aortas was also near side branches and specifically around the celiac artery. Our findings thus support the hypothesis of an early mechanically mediated formation of microstructural defects at aortic branching sites that subsequently propagate into a macroscopic medial tear, giving rise to aortic dissection in angiotensin-II-infused mice.

IL-27 Receptor Signaling potentiates Angiotensin II induced myelopoiesis and promotes Abdominal Aortic Aneurysm

Abstract Abdominal Aortic Aneurysm (AAA) is a vascular disease, where aortic wall degradation is in part mediated by the accumulation of immune cells leading to aortic wall rupture and bleeding which is often fatal for the patient. Smoking, age, male gender, hypertension and atherosclerosis are major risk factors, however the mechanism of AAA development is still elusive. Though cytokines regulate the inflammatory milieu within the aortic wall, their possible role in systemic regulation of this disease, particularly in the control of hematopoietic stem cell proliferation, myeloid cell differentiation and their subsequent accumulation in AAA remains poorly defined. Here we report an unexpected pathogenic role of IL-27R signaling in the development of AAA. We found that in an animal model of AAA, prolonged infusion of Angiotensin (Ang) II robustly induces AAA formation in hyperlipidemic Apoe−/− and Apoe−/−Il27ra+/− mice but not in IL-27R deficient Apoe−/− mice. This mitigation of AAA formation in Apoe−/−Il27ra−/− mice is associated with a blunted accumulation of myeloid cells in suprarenal aortas due to a reduction of Ang II-induced hematopoietic stem and progenitor cell (HSPCs) expansion. We found that the absence of IL-27R signaling engages transcriptional programs that promote HSCs self-renewal program and suppress myeloid lineage differentiation, resulting in decreased mature myeloid cell production and thus a concomitant lack of Ang II-induced myeloid cell accumulation in the suprarenal aortas. Collectively, these data demonstrate that IL-27R signaling influences AAA development by potentiating Ang II induced myelopoiesis and may represent a molecular point of therapeutic intervention in AAA.

Cesarean section in a 17yo with coarctation of suprarenal aorta from takayasu aortitis

Cesarean section in a 17yo with coarctation of suprarenal aorta from takayasu aortitis

Assessing structural and functional response of murine vasculature to acute β-adrenergic stimulation in vivo during hypothermic and hyperthermic conditions

Background: Because of the importance of adrenoreceptors in regulating the cardiovascular (CV) system and the role of the CV system in thermoregulation, understanding the response to these two stressors is of interest. The purpose of this study was to assess changes of arterial geometry and function in vivo during thermal and β-adrenergic stress induced in mice and quantified by MRI.Methods: Male mice were anesthetized and imaged at 7 T. Anatomical and functional data were acquired from the neck (carotid artery), torso (suprarenal and infrarenal aorta and iliac artery) and periphery (femoral artery). Intravenous dobutamine (tail vein catheter, 40 µg/kg/min, 0.12 mL/h) was used as β-adrenergic stressor. Baseline and dobutamine data were acquired at minimally hypothermic (35 °C) and minimally hyperthermic (38 °C) core temperatures. Cross-sectional vessel area and maximum cyclic strain were measured across the cardiac cycle.Results: Vascular response varied by location and by core temperature. For minimally hypothermic conditions (35 °C), average, maximum and minimum areas decreased with dobutamine only at the suprarenal aorta (avg: −17.9%, max: −13.5%, min: −21.4%). For minimally hyperthermic conditions (38 °C), vessel areas decreased between baseline and dobutamine at the carotid (avg: −19.6%, max: −15.5%, min: −19.3%) and suprarenal aorta (avg: −24.2%, max: −17.4%, min: −17.3%); whereas, only the minimum vessel area decreased for the iliac artery (min: −14.4%). Maximum cyclic strain increased between baseline and dobutamine at the iliac artery for both conditions and at the suprarenal aorta at hyperthermic conditions.Conclusions: At hypothermic conditions, the vessel area response to dobutamine is diminished compared to hyperthermic conditions where the vessel area response mimics normothermic dobutamine conditions. The varied response emphasizes the need to monitor and control body temperature during medical conditions or treatments that may be accompanied by hypothermia, especially when vasoactive agents are used.

Gold nanoparticles that target degraded elastin improve imaging and rupture prediction in an AngII mediated mouse model of abdominal aortic aneurysm

Background: Abdominal aortic aneurysms (AAA) are characterized by a progressive disruption and weakening of the extracellular matrix (ECM) leading to dilation of the aorta which can be fatal if not treated. Current diagnostic imaging modalities provides little insight on the varying degree of ECM degeneration that precedes rupture in AAAs. Targeted delivery of contrast agents such as gold nanoparticles (GNPs) that bind to degraded matrix could prove useful when combined with computed tomography (CT) to provide a non-invasive surrogate marker of AAA rupture potential.Methods: AAAs were induced by chronic infusion of angiotensin II (AngII) into low density-lipoprotein receptor-deficient (LDLr -/-) mice in combination with a high-fat diet. Abdominal ultrasound was used to monitor disease progression and to assess the circumferential strain throughout the cardiac cycle. At six weeks, GNPs conjugated with an elastin antibody (EL-GNP) were injected retro-orbitally. Mice were euthanized 24 hours after EL-GNP injection, and aortas were explanted and scanned ex-vivo with a micro-CT system. Histological assessment and 3D models of the aneurysms with micro-CT were used to determine the EL-GNPs distribution. Isolated vessel burst pressure testing was performed on each aneurysmal aorta to quantify rupture strength and to assess rupture location.Results: Aneurysms were found along the suprarenal aorta in AngII infused mice. Darkfield microscopy indicated EL-GNPs accumulation around the site of degraded elastin while avoiding the healthy and intact elastin fibers. Using nonlinear regression, the micro-CT signal intensity of EL-GNPs along the suprarenal aortas correlated strongly with burst pressures (R2=0.9415) but not the dilation as assessed by ultrasound measurements.Conclusions: Using an established mouse model of AAA, we successfully demonstrated in vivo targeting of EL-GNPs to damaged aortic elastin and correlated micro-CT-based signal intensities with burst pressures. Thus, we show that this novel targeting technique can be used as a diagnostic tool to predict the degree of elastin damage and therefore rupture potential in AAAs better than the extent of dilation.

Prevalence of abdominal aorta aneurysm and associated risk factors in Abha city, Saudi Arabia

Objective: The objective was to assess the prevalence and risk factors of abdominal aorta aneurysms (AAAs) in the general population. Materials and Methods: We carried out a prospective, interventional study with patients aged over 60 years screened in the Asir Central Hospital Vascular Department from March 2017 to March 2018. Ultrasound was used to AAA screening. The maximal anteroposterior (AP) and transverse (LL) diameters of the suprarenal and infrarenal aorta were measured in each patient. AAA was defined as aortic dilatation >29 mm in the AP or LL plane. All cases with an aortic diameter >25 mm were included in the study. Results: Our study included 701 patients (531 male, 170 female; age 60–102 years). Most were Saudi nationals (87.6%). There were some smokers (1.3%), 277 (39.5%) had diabetes mellitus, and 233 (31.8%) had hypertension. Fifty-one percent of patient had ischemic heart disease (7.3%), and 13.4% had hypercholesterolemia. Patients were classified into three groups: normal aortic size of 657 patients (93.7%); aortic ectasia 26–29 mm of 24 patients (3.4%); and AAA ≥30 mm of 20 patients (2.9%). The overall prevalence of AAA was ≥30 mm (2.9%) and there is significant relation with hypertension (P Conclusion: Asymptomatic AAA is prevalent in our area. We may need to implement a regular screening program for men aged >60 years, especially high-risk patients to reduce AAA rupture, emergency AAA repair, and mortality.

Dynamic quantitative nonenhanced magnetic resonance angiography of the abdominal aorta and lower extremities using cine fast interrupted steady-state in combination with arterial spin labeling: a feasibility study

BackgroundCine fast interrupted steady-state in combination with arterial spin labeling is a recently described nonenhanced magnetic resonance angiography (MRA) technique that relies on bolus tracking for time-resolved digital subtraction angiography-like displays of blood flow patterns. We evaluated the feasibility of applying this technique to display in-plane flow patterns in two regions: the abdominal aorta and lower extremity peripheral arteries.MethodsWe performed an institutional review board-approved study in healthy subjects and patients. In 7 healthy subjects, in-plane flow was imaged at 4 stations ranging from the lower legs to the aorto-iliac bifurcation (junction of the distal thigh and upper calf, mid-thigh, junction of the upper thigh and pelvis, upper pelvis). In 5 healthy subjects and 6 patients without abdominal aortopathy, images were acquired through the suprarenal abdominal aorta. Ten patients with known peripheral arterial disease and two patients with stable disease of the abdominal aorta were also evaluated. Peak velocity was compared at each of the 4 stations for cine fast interrupted steady-state in combination with arterial spin labeling and two-dimensional cine phase contrast in patients with normal vessels.ResultsIn-plane flow patterns were well visualized in all peripheral arterial stations and in the abdominal aorta, providing a high quality display of hemodynamic patterns along extensive lengths of the vessels. There was very strong positive correlation (r = 0.952, P < 0.05) and excellent agreement (intraclass correlation coefficient, 0.935; 95% confidence interval, 0.812–0.972) between peak flow velocities measured by cine fast interrupted steady-state in combination with arterial spin labeling and two-dimensional cine phase contrast. In 10 patients with peripheral artery disease and 2 patients with aortic pathology, cine fast interrupted steady-state in combination with arterial spin labeling provided a visual demonstration of abnormal hemodynamics.ConclusionThis feasibility study suggests that cine fast interrupted steady-state in combination with arterial spin labeling provides an efficient, high quality and physiologically accurate display of in-plane flow patterns over extensive lengths of the lower extremity peripheral arteries, which can be difficult to achieve using other MRA techniques.

Early pathological characterization of murine dissecting abdominal aortic aneurysms.

We report here on the early pathology of a well-established murine model of dissecting abdominal aortic aneurysms (AAAs). Continuous infusion of angiotensin II (AngII) into apolipoprotein E-deficient mice induces the formation of aortic dissection and expansion at some point after implantation of miniosmotic pumps containing AngII. While this model has been studied extensively at a chronic stage, we investigated the early pathology of dissecting AAA formation at multiple scales. Using high-frequency ultrasound, we screened 12-week-old male mice daily for initial formation of these aneurysmal lesions between days 3 and 10 post-implantation. We euthanized animals on the day of diagnosis of a dissecting AAA or at day 10 if no aneurysmal lesion developed. Aortic expansion and reduced vessel wall strain occurred in animals regardless of whether a dissecting AAA developed by day 10. The aortas of mice that did not develop dissecting AAAs showed intermediate changes in morphology and biomechanical properties. RNA sequencing and gene expression analysis revealed multiple proinflammatory and matrix remodeling genes to be upregulated in the suprarenal aorta of AngII-infused mice as compared to saline-infused controls. Histology and immunohistochemistry confirmed that extracellular matrix remodeling and inflammatory cell infiltration, notably neutrophils and macrophages, occurred in AngII-infused mice with and without dissecting AAAs but not saline-infused controls. Understanding early disease processes is a critical step forward in translating experimental results in cardiovascular disease research. This work advances our understanding of this well-established murine model with applications for improving early diagnosis and therapy of acute aortic syndrome in humans.

SR1001 confers protection against the experimental abdominal aortic aneurysm induced by angiotensin II in ApoE-/-mice

Objective To investigate the effect and mechanism of SR1001 treatment in angiotensin Ⅱ (AngⅡ) induced experimental abdominal aortic aneurysm (EAAA) in apolipoprotein E (ApoE-/-) mice. Methods Forty-five male apolipoprotein E-deficient (ApoE-/-) mice were randomly divided into the following 3 groups: Sham group, AngⅡ model group (Control group), AngⅡ+ SR1001 treatment group (SR1001 group). All mice were treatment with 0.5% dimethylsurfoxide (DMSO) or SR1001 by intraperitoneal injection. The aortic diameter was measured via ultrasound imaging, and the suprarenal aorta was chosen as the measuring point on days 0, 14, 28 thereafter. Twenty-eight days after AngⅡ infusion, the abdominal aortic specimens were harvested. The elastica van Gieson (EVG) staining, and immunofluorescent staining were performed for histopathologic analysis. The protein levels of interleukin (IL)-17, monocyte chemotactic protein (MCP)-1, interferon (IFN)-γ were determined by Western blotting analysis. Results (1) Compared with the Control group, the AAA incidence in the SR1001 group was significantly reduced (33.3% vs. 73.3%, χ2=4.821, P=0.028), Abdominal aorta diameter [(1.39±0.06) mm vs. (1.98±0.11) mm, P=0.009]. However, there was no significant difference in abdominal aorta diameter between the SR1001 group and Sham group [(1.39±0.06) mm vs. (1.07±0.08) mm, P=0.064]. (2) SR1001 treatment in SR1001 group preserves the structure of the aortic wall (P=0.018). (3) SR1001 treatment in SR1001 group attenuates local inflammatory cell infiltration in the EAAA model. (4) SR1001 treatment in SR1001 group suppresses the protein expression of pro-inflammatory mediators (IL-17, MCP-1, IFN-γ) in the EAAA model (P=0.008, 0.016, 0.023, respectively). Conclusion Treatment with SR1001 inhibits the Th17/IL-17A-related inflammatory responses, preserves the structure of the aortic wall, reduces local inflammatory cell infiltration and inflammatory factors expression, and attenuates the progression of abdominal aortic aneurysm. Key words: SR1001; Angiotensin Ⅱ; Apolipoprotein E-/-mice; Interleukin-17; Inflammatory cell; Experimental abdominal aortic aneurysm

Abstract 17183: Genetically Engineered Calcification Increases Surface Roughness and Changes the Distribution of Atherosclerotic Plaques in Mice With Atherosclerosis

Background: Atherosclerosis is an inflammatory disease that contributes significantly to cardiovascular mortality. Arterial stiffening due to calcification can coexist with or directly influence pathogenesis of atherosclerosis. We hypothesize that arteriosclerosis caused by genetically engineered calcification in mice redistributes shear stress on the endothelial cells, which in turn leads to further accelerated rate of plaque formation. Methods: All of the mice had an LDL receptor mutation and were fed pro-atherogenic diet (1.25% cholesterol). The case group overexpressed tissue-nonspecific alkaline phosphatase in endothelial cells (eTNAP). The luminal surfaces of descending thoracic aorta (TA) and suprarenal abdominal aorta (AA) were scanned using Sensofar S Neox optical confocal microscope at 1 μm vertical resolution. The surface topographies per sample, each measuring 500 x 700 microns, were analyzed for ISO 25178-2 areal roughness parameters using SensoMap. Parameters were compared by t test (n=5 eTNAP, n=6-7 control). Results: We observed a significant difference in the incidence as well as the morphology of the plaques in the eTNAP group compared to control mice. There was a 4.8 fold increase in the number of topological motifs in the thoracic aorta of the eTNAP vs. controls (p &lt; 0.01). Similarly, the number of motifs was increase in the abdominal aorta of the eTNAP mice compared to controls (2.8 fold; p=0.06). The average area of the motifs was significantly larger in the controls compared to the eTNAP group in both segments of the aorta (p=0.06 TA; p &lt; 0.05 AA). The maximum height of the lesions in the TA was not different between the groups (p=0.62), however increased by 74% in the abdominal aorta of the eTNAP compared to controls (p&lt;0.05). Finally, the surface developed interfacial area ratio (Sdr, a parameter of texture) was increased in the eTNAP group in both the TA (p &lt; 0.05) and AA regions (p &lt; 0.01). Conclusion: Arteriosclerosis increases surface roughness. In our model, the abdominal region had a high incidence of taller, irregular lesions whereas those in the thoracic aorta were flatter and more spaced. The high resolution scans will be further used to study the hemodynamic disturbances to the endothelial cells using flow dynamics simulations.

Arterial Phase CTA Replacement by a Virtual Arterial Phase Reconstruction from a Venous Phase CTA: Preliminary Results Using Detector-Based Spectral CT.

To assess the feasibility of creating virtual monoenergetic arterial images from venous phase CTA obtained on a detector-based spectral CT scanner and quantitatively compare the signal-to-noise (SNR) and contrast-to-noise (CNR) ratios of the major arteries to those on polyenergetic true arterial phase images. In this retrospective study, 23 patients (15 men and 8 women, median age 68years) who underwent triple-phase CTA on a spectral CT scanner for aortic endograft surveillance were included. The venous phase CTA of each study was reconstructed to generate virtual monoenergetic images at various keV, which were compared to true arterial phase CTA images. SNR and CNR of the aortoiliac arteries were evaluated by testing the differences in means and non-inferiority of virtual arterial images to true arterial images. Effective radiation dose was calculated for standard triple-phase studies in comparison with dual-phase and single-phase spectral CT examinations. Virtual monoenergetic images demonstrated non-inferior (P < 0.05) arterial SNR and CNR compared to true arterial images at 40keV for all arteries, at 45-50keV for the thoracic and suprarenal aorta, and at 45-55keV for the infrarenal aorta and iliac arteries. Significantly higher (P < 0.05) arterial attenuation was obtained at 40keV for the aortoiliac arteries. Mean effective dose for conventional triple-phase studies was 32.5mSv in comparison with 21.3mSv for dual-phase non-contrast/venous scans and 11.3mSv for single-phase venous scans. Detector-based spectral CT enables creation of virtual monoenergetic arterial images from venous phase CTA with equivalent and in some cases significantly higher SNR/CNR of major arteries compared to images from true arterial phase polyenergetic CTA.

TAA8. Aortic Epithelioid Angiosarcoma After Endovascular Treatment of Descending Aortic Ulcer

Aortic epithelioid angiosarcoma is a rare disease. We report a case of epithelioid angiosarcoma of the abdominal aortic wall after endovascular treatment of descending aortic ulcer. A 55-year-old man, diagnosed with descending aortic ulcer through regular health examination, was implanted with a Gore Conformable TAG (W. L. Gore & Associates, Flagstaff, Ariz) at the suprarenal aorta, with celiac trunk covered. During 4-month follow-up, the patient had no complaints, and no graft migration was shown by computed tomography angiography (CTA) examination, yet superior mesenteric artery occlusion was observed. During 10-month follow-up, the patient presented with abdominal back pain, general fatigue, and fever. CTA examination showed abnormal density around the graft, which was assumed to be a graft infection with periaortic tissue compatible with an inflammatory reaction. After invalid treatment for infection, positron emission tomography-computed tomography was performed and showed avid fluorodeoxyglucose uptake at the descending aorta, retroperitoneum, right lung, pancreas, spleen, left kidney, mesenteric glands, and left whirl bone. Computed tomography-guided biopsy confirmed it as epithelioid angiosarcoma. On review of the CTA study, no sign of malignant tumor was found on the preoperative images; however, left renal metastases were seen on the 4-month postoperative images. There may have been an association between angiosarcoma and artificial graft observed in animal experiments or rare cases before. However, this is the first case of epithelioid angiosarcoma after Conformable TAG aortic endograft placement. In addition, the rapid onset of the tumor also confused us as to whether the cause of the descending aortic ulcer was arteriosclerosis or epithelioid angiosarcoma and whether the epithelioid angiosarcoma was primary or secondary to the artificial graft.

A Novel Paradigm for Sacubitril/Valsartan: Beta-Endorphin Elevation as a Contributor to Exercise Tolerance Improvement in Rats With Preexisting Heart Failure Induced by Pressure Overload

BackgroundSimultaneous angiotensin receptor (AT1) blockade and neprilysin inhibition with the use of sacubitril/valsartan has been recently approved to treat patients with heart failure (HF). Therapeutic benefits of this therapy have been attributed to natriuretic peptide elevation and AT1 receptor blockade. However, that pharmacologic picture may not be complete. The aims of this study were to investigate the pharmacology of sacubitril/valsartan compared with sacubitril and valsartan alone and to examine their impact on peptides up-regulated by neprilysin inhibition, such as beta-endorphin. Methods and ResultsAn HF model was induced by pressure overload via constriction of the suprarenal abdominal aorta in rats. Sacubitril/valsartan (68 mg/kg), valsartan (31 mg/kg), sacubitril (31 mg/kg), or placebo was administered by daily oral gavage (starting 4 weeks after pressure overload onset and continued for 4 additional weeks; n = 8 in each group). Exercise tolerance testing was conducted using a rodent treadmill and hemodynamic assessments were conducted under anesthesia with the use of Millar left ventricular (LV) conductance technology. Pressure overload led to exercise intolerance by 4 weeks and to hypertension and LV dysfunction and remodeling by 8 weeks. Both sacubitril/valsartan and sacubitril elevated beta-endorphin levels, by 40% and 54%, respectively, and improved exercise tolerance, by 93% and 112%, whereas valsartan did not. Indices of LV dysfunction persisted with the use of sacubitril/valsartan and valsartan therapies and even deteriorated in sacubitril group. ConclusionsWhen added to valsartan, sacubitril increases beta-endorphin concentrations and improves exercise tolerance. These data suggest beta-endorphin elevation as a potential mechanism of action leading to improvement in exercise tolerance that is seen with sacubitril/valsartan. This therapeutic benefit is potentially independent from LV function.