UNASSIGNED: Most abdominal aortic aneurysms (AAAs) are small with low rupture risk (<1%/y) when diagnosed but slowly expand to ≥55 mm and undergo surgical repair. Patients and clinicians require medications to limit AAA growth and rupture, but drugs effective in animal models have not translated to patients.
UNASSIGNED: Use models that simulate human AAA tissue pathology, growth patterns, and rupture; focus on the clinically relevant outcomes of growth and rupture; design studies with the rigor required of human clinical trials; monitor AAA growth using reproducible ultrasound; and perform studies in both males and females.
UNASSIGNED: The aortic adventitial elastase oral β-aminopropionitrile model has many strengths including simulating human AAA pathology and modeling prolonged aneurysm growth. The Ang II (angiotensin II) model performed less well as it better simulates acute aortic syndrome than AAA. The elastase plus TGFβ (transforming growth factor-β) blocking antibody model displays a high rupture rate, making prolonged monitoring of AAA growth not feasible. The elastase perfusion and calcium chloride models both display limited AAA growth.

An increased prevalence of vascular calcification (VC) has been reported in kidney stone formers (KSFs), along with an elevated cardiovascular risk. The aim of the current study is to assess whether VC in these patients develops at a younger age and is influenced by stone composition. This single-center, matched case-control study included KSFs with uric acid or calcium oxalate stones (diagnosed based on stone analysis) and age- and sex-matched controls without a history of nephrolithiasis. The prevalence and severity of abdominal aortic calcification (AAC) and bone mineral density (BMD) were compared between KSFs and non-KSFs. In total, 335 patients were investigated: 134 with calcium oxalate stones, 67 with uric acid stones, and 134 controls. Overall, the prevalence of AAC was significantly higher among calcium stone formers than among the controls (67.9% vs. 47%, p = 0.002). In patients under 60 years of age, those with calcium oxalate stones exhibited both a significantly elevated AAC prevalence (61.9% vs. 31.3%, p = 0.016) and severity (94.8 ± 15.4 vs. 30.3 ± 15.95, p = 0.001) compared to the controls. Within the age group of 40-49, osteoporosis was identified only in the KSFs. Multivariate analysis identified age, smoking, and the presence of calcium stones as independent predictors of AAC. This study highlights that VC and osteoporosis occur in KSFs at a younger age than in non-stone-formers, suggesting potential premature VC. Its pathogenesis is intriguing and needs to be elucidated. Early evaluation and intervention may be crucial for mitigating the cardiovascular risk in this population.

Glutamine (Gln), known as the most abundant free amino acid, is widely spread in human body. In this study, we demonstrated the protective effects of glutamine against mouse abdominal aortic aneurysm (AAA) induced by both angiotensin II (AngII) and calcium phosphate (Ca3(PO4)2) in vivo, which was characterized with lower incidence of mouse AAA. Moreover, histomorphological staining visually presented more intact elastic fiber and less collagen deposition in abdominal aortas of mice treated by glutamine. Further, we found glutamine inhibited the excessive production of reactive oxide species (ROS), activity of matrix metalloproteinase (MMP), M1 macrophage activation, and apoptosis of vascular smooth muscle cells (VSMCs) in suprarenal abdominal aortas of mice, what\'s more, the high expressions of MMP-2 protein, MMP-9 protein, pro-apoptotic proteins, and IL-6 as well as TNF-α in protein and mRNA levels in cells treated by AngII were down-regulated by glutamine. Collectively, these results revealed that glutamine protected against mouse AAA through inhibiting apoptosis of VSMCs, M1 macrophage activation, oxidative stress, and extracellular matrix degradation.

BACKGROUND: Recent studies suggest that immune-mediated inflammation of perivascular adipose tissue of abdominal aortic aneurysms (AAAs) contributes to disease development and progression. Whether the perivascular adipose tissue of AAA is characterized by a specific adaptive immune signature remains unknown.
RESULTS: To investigate this hypothesis, we sequenced the T-cell receptor β-chain in the perivascular adipose tissue of patients with AAA and compared it with patients with aortic occlusive disease, who share the former anatomical site of the lesion and risk factors but differ in pathogenic mechanisms. Our results demonstrate that patients with AAA have a lower repertoire diversity than those with aortic occlusive disease and significant differences in variable/joining gene segment usage. Furthermore, we identified a set of 7 public T-cell receptor β-chain clonotypes that distinguished AAA and aortic occlusive disease with very high accuracy. We also found that the T-cell receptor β-chain repertoire differentially characterizes small and large AAAs (aortic diameter<55 mm and ≥55 mm, respectively).
CONCLUSIONS: This work supports the hypothesis that T cell-mediated immunity is fundamental in AAA pathogenesis and opens up new clinical perspectives.

Waist-to-height ratio (WtHR) is a validated biomarker of central obesity that appears to be preferable to other body composition measurements in the evaluation of cardiovascular disease. The goal of this research was to explore the connection between WtHR and abdominal aortic calcification (AAC) among adults. On the basis of data from the 2013 to 2014 National Health and Nutrition Examination Survey, multivariate logistic regression, sensitivity analysis, as well as smoothed curve fitting were used to evaluate the connection between WtHR and AAC. Subgroup analyses along with interaction tests were done to see if this link was consistent across populations. Among 3079 participants aged >40 years, there was a negative association between WtHR and ACC. Each 1-unit emergence of WtHR was related to a 2% reduction in the probability of severe AAC in the entirely adjusted model (odds ratio = 0.02, 95% confidence interval: [0.00-0.12]). Participants in the highest WtHR quartile were 39% less likely to acquire severe AAC compared with those in the lowest quartile. (odds ratio = 0.61, 95% confidence interval: [0.37-1.00]). This negative association was more pronounced in the diabetes subgroup. We discovered a reversed U-shaped association between WtHR as well as AAC score utilizing a 2-stage linear regression model, with an intersection point of 0.56. WtHR was negatively associated with AAC among US adults.

Inflammation induced by activated macrophages within vulnerable atherosclerotic plaques (VAPs) constitutes a significant risk factor for plaque rupture. Translocator protein (TSPO) is highly expressed in activated macrophages. This study investigated the effectiveness of TSPO radiotracers, 18F-FDPA, in detecting VAPs and quantifying plaque inflammation in rabbits. 18 New Zealand rabbits were divided into 3 groups: sham group A, VAP model group B, and evolocumab treatment group C. 18F-FDPA PET/CTA imaging was performed at 12, 16, and 24 weeks in all groups. Optical coherence tomography (OCT) was performed on the abdominal aorta at 24 weeks. The VAP was defined through OCT images, and ex vivo aorta PET imaging was also performed at 24 weeks. The SUVmax and SUVmean of 18F-FDPA were measured on the target organ, and the target-to-background ratio (TBRmax) was calculated as SUVmax/SUVblood pool. The arterial sections of the isolated abdominal aorta were analyzed by HE staining, CD68 and TSPO immunofluorescence staining, and TSPO Western blot. The results showed that at 24 weeks, the plaque TBRmax of 18F-FDPA in group B was significantly higher than in groups A and C. Immunofluorescence staining of CD68 and TSPO, as well as Western blot, confirmed the increased expression of macrophages and TSPO in the corresponding regions of group B. HE staining revealed an increased presence of the lipid core, multiple foam cells, and inflammatory cell infiltration in the area with high 18F-FDPA uptake. This indicates a correlation between 18F-FDPA uptake, inflammation severity, and VAPs. The TSPO-targeted tracer 18F-FDPA shows specific uptake in macrophage-rich regions of atherosclerotic plaques, making it a valuable tool for assessing inflammation in VAPs.

UNASSIGNED: Ischemia-reperfusion (IR) injury to a part of the body can cause damage to distant organs such as the kidney and heart. This study investigated the protective effects of safranal against IR-induced renal injury.
UNASSIGNED: Used in this study were 24 Wistar Albino male rats, which were divided into 3 equal and randomised groups. The sham group underwent laparotomy only. In the IR group, the infrarenal aorta was clamped for 1 h, and then reperfused for 2 h. In the IR-safranal group, safranal was administered 30 min before the procedure and IR injury was induced in the same way as in the IR group. After the procedure, blood and tissue samples were collected from the rats for biochemical and histopathological analyses. Antioxidant capacity and proinflammatory cytokine analyses were performed on the blood samples. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining was performed to determine the number of cells undergoing apoptosis in the kidney tissue.
UNASSIGNED: The estimated glomerular filtration rate, an indicator of renal function, was lower in the IR group (p1 = 0.024 vs. p3 = 0.041, respectively) compared to the other groups, while creatinine levels were higher in the IR group compared to the other groups (p1 = 0.032 vs. p2 = 0.044, respectively). The blood urea nitrogen level was higher in the IR group than in the other groups (p1 = 0.001vs p2 = 0.035, respectively). The total antioxidant and total oxidant status, indicating tissue oxidative stress, did not differ between groups (p = 0.914 vs. p = 0.184, respectively). Among the proinflammatory cytokines, the interleukin-1β (IL-1β) and IL-6 levels were significantly higher in the IR group (p = 0.034 vs. p = 0.001, respectively), but the tumour necrosis factor-α (p = 0.19), and interferon-γ (p = 0.311) levels did not differ between groups. Histopathological examination showed significantly less damage to glomerular and tubular cells in the IR-safranal group (p < 0.001). The number of TUNEL-positive cells was higher in the IR group compared to the other groups (p < 0.001).
UNASSIGNED: Safranal may have protective effects against kidney damage caused by distant ischemia-reperfusion injury.

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

Distinguishing quiescent from rupture-prone atherosclerotic lesions has significant translational and clinical implications. Electrochemical impedance spectroscopy (EIS) characterizes biological tissues by assessing impedance and phase delay responses to alternating current at multiple frequencies. We evaluated invasive 6-point stretchable EIS sensors over a spectrum of experimental atherosclerosis and compared results with intravascular ultrasound (IVUS), molecular positron emission tomography (PET) imaging, and histology. Male New Zealand White rabbits (n = 16) were placed on a high-fat diet, with or without endothelial denudation via balloon injury of the infrarenal abdominal aorta. Rabbits underwent in vivo micro-PET imaging of the abdominal aorta with 68Ga-DOTATATE, 18F-NaF, and 18F-FDG, followed by invasive interrogation via IVUS and EIS. Background signal-corrected values of impedance and phase delay were determined. Abdominal aortic samples were collected for histology. Analyses were performed blindly. EIS impedance was associated with markers of plaque activity including macrophage infiltration (r = .813, p = .008) and macrophage/smooth muscle cell (SMC) ratio (r = .813, p = .026). Moreover, EIS phase delay correlated with anatomic markers of plaque burden, namely intima/media ratio (r = .883, p = .004) and %stenosis (r = .901, p = .002), similar to IVUS. 68Ga-DOTATATE correlated with intimal macrophage infiltration (r = .861, p = .003) and macrophage/SMC ratio (r = .831, p = .021), 18F-NaF with SMC infiltration (r = -.842, p = .018), and 18F-FDG correlated with macrophage/SMC ratio (r = .787, p = .036). EIS with phase delay integrates key atherosclerosis features that otherwise require multiple complementary invasive and non-invasive imaging approaches to capture. These findings indicate the potential of invasive EIS to comprehensively evaluate human coronary artery disease.

OBJECTIVE: To evaluate the long-term influence of preoperative invasive coronary screening and preventive myocardial revascularization on mortality and cardiac complications after open surgery for abdominal aortic aneurysms (AAA).
METHODS: We present long-term outcomes after open surgery for AAA between 2011 and 2022. Patients without clinical or objective signs of coronary artery disease were included. In the 1st group, routine coronary angiography was performed before surgery. Prophylactic myocardial revascularization was performed in 12 cases. Long-term data on 45 patients were obtained. In the 2nd group, 53 patients underwent repair without invasive coronary screening, and data on 48 patients were obtained in this group.
RESULTS: The median follow-up was 32 and 79 months, respectively. Kaplan-Meyer overall 48-month survival was 87.3% and 82.1%, respectively (p=0.278). In the first group, 2 patients developed angina pectoris in the same period. In the second group, we observed 2 cases of myocardial infarction and 3 cases of angina pectoris without infarction. Analysis of survival curves found no significant differences (p=0.165).
CONCLUSIONS: In our study, invasive coronary screening and preventive myocardial revascularization in patients without clinical and objective signs of coronary artery did not improve 4-year long-term period after abdominal aortic repair. Perhaps, differences will appear after 4 years, and this requires further follow-up after coronary angiography. However, there is a tendency towards more common onsets of coronary artery disease that dictates the need for cardiac monitoring of such patients.
В современной литературе все чаще поднимается вопрос об инвазивной оценке коронарного русла и профилактической реваскуляризации миокарда пациентам перед сосудистыми вмешательствами.
UNASSIGNED: Оценить отдаленные результаты резекции аневризмы брюшной аорты с позиции влияния предоперационного инвазивного коронарного скрининга и профилактической реваскуляризации миокарда на летальность и развитие кардиальных осложнений.
UNASSIGNED: Представляем отдаленные результаты исследования пациентов, которым с 2011 по 2022 г. выполнена резекция аневризмы брюшной аорты. В исследование включены больные, не имевшие клинических или инструментальных проявлений ишемической болезни сердца. В 1-й группе 50 пациентам до операции проводили рутинную коронарографию (КАГ), в дальнейшем в 12 случаях потребовалась профилактическая реваскуляризация миокарда. Получены отдаленные данные о 45 больных. Пятьдесят три пациента из 2-й группы были прооперированы без инвазивного исследования коронарных артерий, в этой группе получена информация о 48 больных.
UNASSIGNED: Медиана наблюдения в 1-й группе составила 32 мес, во 2-й — 79 мес. Кумулятивная выживаемость в течение 48 мес в 1-й группе составила 87,3%, в группе без КАГ — 82,1%, анализ кривых выживаемости по Каплан—Мейеру значимых различий не выявил (p=0,278). В 1-й группе за тот же срок у 2 пациентов дебютировала ишемическая болезнь сердца (ИБС) в виде стенокардии напряжения. Во 2-й группе зафиксировано 2 случая инфаркта миокарда и 3 случая стенокардии без инфаркта. При анализе кривых выживаемости значимых различий также не выявлено (p=0,165).
UNASSIGNED: В нашем исследовании среди пациентов без клинических проявлений и инструментальных признаков ишемической болезни сердца тактика рутинной коронарографии и профилактической реваскуляризации миокарда существенно не улучшила течение 4-летнего отдаленного периода после резекции аневризмы брюшной аорты. Возможно, различия появятся после 4 лет, это требует дальнейшего наблюдения больных после КАГ. Тем не менее имеется тенденция к увеличению частоты дебютов ИБС в этот период, что диктует необходимость кардиологического мониторинга таких пациентов.