Aortic Lesions Research Articles

Endovascular Repair of Zone 0 Ascending Aortic Aneurysm: A Review of Current Knowledge and Developing Technology.

Aortic aneurysms represent the 15th leading cause of death in men and women over 55 years of age. Where historically these lesions were all addressed via an open approach, endovascular aortic repair has entirely altered the way that surgeons approach aortic lesions. Although it was initially employed for patients who were poor surgical candidates, endovascular repair is now standard for abdominal aortic aneurysms and aneurysms in the descending thoracic aorta. Open surgery remains the gold standard for management of ascending aneurysms, in part due to the limitations portended by the anatomy of the ascending aorta, although increasing evidence suggests that endovascular approaches are feasible and may sometimes be optimal for patient outcomes. Here, we present some of the anatomical and technical challenges of the endovascular approach to these "Zone 0" aneurysms, the associated complications, and the current state of device development.

Results of surgical treatment of infective endocarditis complicated by acute heart failure

Objective. To evaluate the results of surgical treatment of infective endocarditis complicated by acute heart failure. Materials and methods. The clinical data of 72 patients with infective endocarditis complicated by preoperative acute heart failure who underwent cardiac surgery at the Amosov National Institute of Cardiovascular Surgery of the National Academy of Medical Sciences of Ukraine from 01.01.2019 to 30.12.2022 were studied. All patients were assigned to functional class IV according to the functional classification of the New York Heart Association. Results. The average duration of infective endocarditis from its first signs (hyperthermia above 38 °C) to diagnosis was 2 months (2; 4 months). Among the causes of infective endocarditis, bronchopulmonary diseases dominated – 24 (33.3%) observations, general surgical interventions – 7 (9.7%) and hospital infection – 7 (9.7%). Urologic surgical interventions caused the development of infective endocarditis in 6 (8.3%) patients, hypothermia in 4 (5.6%), drug addiction in 4 (5.6%), and dental procedures in 1 (1.4%) patient. In 19 (26.4%) patients, the causes of infective endocarditis were not established. In 62 (86.1%) patients, a multi–valve correction was performed, and in 10 (13.9%) – a single–valve correction. The most common were two main options: aortic valve prosthetics in combination with mitral and tricuspid valve surgery in 13 (18.1%) patients and mitral and tricuspid valve surgery in 14 (19.4%) patients. Surgical intervention for combined lesions of the valvular apparatus of the left and right heart was performed in 51 (70.8%) patients with infective endocarditis complicated by acute heart failure. Frequent intracardiac abscessing – in 20 (27.8%) patients with aortic valve lesions and in 9 (12.5%) patients with mitral valve lesions – indicated a high rate of extensive infection spread. Hospital mortality in the surgical treatment of infective endocarditis complicated by acute heart failure was 13.9%. 10 patients died. Conclusions. In 96.1% of patients with infective endocarditis complicated by preoperative acute heart failure, multivalve surgical correction was performed. In the initial acute heart failure in the setting of infective endocarditis, intracardiac abscessing was often recorded: 27.8% in aortic valve lesions and 12.5% in mitral valve lesions. Hospital mortality in the surgical treatment of infective endocarditis complicated by preoperative acute heart failure was 13.9%.

Abstract 4138348: Mechanical stress-mediated nuclear envelope damage promotes Aortic Valve Calcification through the ZBP1-RIPK3-NF-κB signaling axis

Methods and Results: We describe a comprehensive characterization of the AVICs nucleus landscape as determined by transmission electron microscopy (TEM) of samples obtained from CAVD patients. Turbulence led to nuclear envelope integrity lose in AVICs cultured in shear stress experiments, with three different fluid conditions [static (ST), laminar stress (LS), and oscillatory stress (OS)], indicated by Western blot and immunofluorescence (IF). Silencing lamin A/C (LMNA) through small interfering RNA (siRNA), accelerated nuclear envelope damage , as indicated by Western blot, qPCR, and immunofluorescence (IF). The formation of Z-DNA and its co-localization with Z-DNA binding protein (ZBP1) was observed due to the nuclear envelope damage by IF. Western blot, qPCR, IHC and IF confirmed Z-DNA-induced inflammation in AVICs through the ZBP1-RIPK3-NF-κB signaling pathway. ZBP1 and RIPK3 knockdown with siRNA markedly reduced the protein level of osteogenic markers alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2), and bone morphogenetic protein 2 (BMP2) in VICs. In vivo, aortic valve disease was constructed by direct wire injury (DWI), and we showed that overexpression of LMNA by adeno-associated virus significantly decelerated the progression of aortic valve lesion induced by DWI in mice. Conclusion: Excessive mechanical stress can induce damage to the nuclear envelope of AVICs by causing cytoskeletal remodeling, initiating the formation of Z-DNA, and hastening the calcification process in AVICs and CAVD.

Abstract 4131674: ADP-Ribosylation In a Mouse Model of Atherosclerosis: a Potential Novel Link Between Dyslipidemia and Inflammation in Cardiovascular Disease

Background: Inflammation and lipid accumulation are major features of atherosclerosis, a leading cause of death and morbidity worldwide. Our previous study recognized ADP-ribosylation, a post-translational modification, as a novel regulator of macrophage activation. We also have established mass spectrometry-based ADP-ribosylation proteomics. Using this technology, we evaluated the completely uncharacterized role of ADP-ribosylation in atherogenesis. We hypothesized that ADP-ribosylated proteins circulate from liver, accumulate in aorta and promote atherogenesis. Methods and Results: We harvested the aorta, liver, and plasma of LDL receptor-deficient ( Ldlr -/- ) mice that were on a regular chow or high-fat diet for 3 or 6 months (n=40/condition). To increase ADP-ribosyl peptide signals in the aorta, we applied our novel recently optimized ion mobility mass spectrometry strategy to generate ADP-ribosylation proteomics data. We analyzed 160 mice aortas and identified 3 APOA1 and 3 APOE ADP-ribosylated peptides in both the aorta and the liver (Fig. A). In addition, these peptides were differentially abundant in the aorta of HFD-fed mice, compared to controls (i.e, APOA1 ARPALEDLR peptide relative abundance (Fig. B)). Using the same mouse plasma, we then validated the presence of ADP-ribosylated APOA1 and ADP-ribosylated APOE in HDL and chylomicron/VLDL/LDL fractions (Western blot), respectively. This finding indicates that classical apolipoproteins circulate as ADP-ribosylated forms, representing a completely novel class of modified apolipoproteins. Immunohistochemistry confirmed the enrichment of aortic lesions in macrophages and ADP-ribosylation signal (5-fold increase, p=0.0006). Conclusions: This work provides the first in vivo evidence that ADP-ribosylation occurs in atherosclerotic lesions, which may originate from the liver via circulating blood (Fig. C). Future studies will examine whether ADP-ribosylation of apolipoproteins, specifically APOA1, alters anti-atherogenic functions of HDL.

Initial results of the Hyperion IIDPET insert for simultaneous PET-MRI applied to atherosclerotic plaque imaging in New-Zealand white rabbits.

In preclinical research, in vivo imaging of mice and rats is more
common than any other animal species, since their physiopathology is very well-
known and many genetically altered disease models exist. Animal studies based on
small rodents are usually performed using dedicated preclinical imaging systems
with high spatial resolution. For studies that require animal models such as mini-
pigs or New-Zealand White (NZW) rabbits, imaging systems with larger bore
sizes are required. In case of hybrid imaging using Positron Emission Tomography
(PET) and Magnetic Resonance Imaging (MRI), clinical systems have to be used,
as these animal models do not typically fi t in preclinical simultaneous PET-MRI
scanners.
Approach. In this paper, we present initial imaging results obtained with the
Hyperion IID PET insert which can accommodate NZW rabbits when combined
with a large volume MRI RF coil. First, we developed a rabbit-sized image
quality phantom of comparable size to a NZW rabbit in order to evaluate the
PET imaging performance of the insert under high count rates. For this phantom,
radioactive spheres with inner diameters between 3.95 and 7.86 mm were visible
in a warm background with a tracer activity ratio of 4.1 to 1 and with a total
18-F activity in the phantom of 58MBq at measurement start. Second, we performed
simultaneous PET-MR imaging of atherosclerotic plaques in a rabbit in vivo using
a single injection containing 18-F-FDG for detection of infl ammatory activity,
and Gd-ESMA for visualization of the aortic vessel wall and plaques with MRI.
Main results. The fused PET-MR images reveal 18-F-FDG uptake within an
active plaques with plaque thicknesses in the sub-millimeter range. Histology
showed colocalization of 18-F-FDG uptake with macrophages in the aortic vessel wall lesions. 
Significance. Our initial results demonstrate that this PET insert
is a promising system for simultaneous high-resolution PET-MR atherosclerotic
plaque imaging studies in NZW rabbits.

Cardioprotective potential of oleuropein, hydroxytyrosol, oleocanthal and their combination: unravelling complementary effects on acute myocardial infarction and metabolic syndrome

Abstract Background/Introduction Clinical studies have established the role of olive products in primary and secondary prevention of cardiovascular (CV) disease, but the single compounds or compound combinations responsible for the protective effects are still under investigation. Purpose We sought to explore and compare the cardioprotective potential of Oleuropein (OL), Hydroxytyrosol (HT), Oleocanthal (OC) and Oleanolic Acid (OA) and three combinational treatments after chronic oral administration in mice subjected to Ischemia/Reperfusion Injury (IRI) in the presence of metabolic syndrome (MS) and verify the effect of combination in a proof-of-concept clinical study in Chronic Coronary Artery Syndrome (CCAS) patients. Methods First, we explored the IRI-limiting potential of 6-weeks daily oral treatment with OL (20.6 mg/kg), HT (5.9 mg/kg), OC (11.6 mg/kg), OA (17.4 mg/kg) or vehicle (DMSO 5%) in healthy C57Bl6 mice. At week 6, myocardial ischemia/reperfusion (30 minutes/2 hours) was induced and infarct size was measured. Next, MS was established by 14 weeks of Western diet and the isolated compounds were administered for the last 6 weeks. At week 14, IRI was surgically induced, and infarct size was determined. Basic MS parameters (fasting blood glucose, plasma cholesterol, body weight and blood pressure) were recorded at baseline, weeks 8 and 14. According to the exerted benefits, three combinational treatments were designed and tested on the MS model of IRI. The underlying cardioprotective mechanism was investigated on the mixture with preponderant CV benefits (OL-HT-OC, Combo 2). ApoE-/- mice fed with Western diet for 12 weeks were treated with Combo 2 orally for the last 4 weeks and aortic atherosclerotic lesion extent was determined to detect possible antiatherosclerotic effects. After multi-organ toxicity evaluation, a Combo 2-based supplement was administered in CCAS patients for evaluation of cardiac function, inflammation and oxidative stress biomarkers. Results OL, OC and OA, but not HT, significantly reduced infarct size in vivo both in healthy and MS mice. OL was the only compound to reduce hyperglycemia, while OA significantly reduced plasma cholesterol. All mixtures (Combo 1: OL-HT-OA, Combo 2: OL-HT-OC, Combo 3: OL-HT-OC-OA) were cardioprotective, but only Combo 2 prevented MS progression by limiting hyperglycemia. Combo 2 protection against IRI was attributed to apoptosis suppression (reduced Bax/BcL-xL ratio) and increased expression of the antioxidant enzymes Superoxide Dismutase and Catalase in the ischemic myocardium. Combo 2 treatment also reduced atherosclerotic lesion extent. In our proof-of-concept clinical study, Combo 2 treatment ameliorated cardiac, vascular and endothelial function in CCAS patients. Conclusions Combinational treatment with OL-HT-OC exerts potent cardioprotective, antihyperglycemic and antiatherosclerotic properties in vivo, with remarkable and clinically translatable CV benefits in high-risk patients.

The orchestration of coding and non-coding genes at the CDH13 locus in coronary artery disease

Abstract Background The CDH13 locus was associated with coronary artery disease (CAD) by genome-wide association studies (GWAS). However, the causal gene(s) and underlying disease mechanisms at this locus remain undetermined. Purpose We intended to pinpoint and functionally validate the causal coding and non-coding genes at the CDH13 locus and delineate the underlying mechanisms for CAD. Methods and results We conducted the transcriptome-wide association analysis (TWAS) using nine types of CAD-relevant tissues from Stockholm-Tartu Atherosclerosis Reverse Network Engineering Task (STARNET) and Genotyped Tissue Expression (GTEx) projects and identified CDH13 (T-cadherin) and four long non-coding RNA (lncRNA) genes as candidate causal genes at The CDH13 locus. One of the antisense(AS) lncRNAs, CDH13-AS2, was predicted to bind on the 3’ untranslated region (UTR) of CDH13 using LncRRIsearch and RNAup servers. The binding interaction was validated by dCas13-medicated RNA immunoprecipitation. Weighted correlation network analysis (WGCNA) using transcriptomic data from CAD-relevant tissues of ~600 human subjects suggested a positive expression correlation between CDH13 and CDH13-AS2 in artery tissues. CRISPR/Cas9-based knockout (KO) of CDH13 or CDH13-AS2 in human umbilical vein endothelial cells (HUVECs) indicated synergistically atherogenic phenotypes, including reduced proliferation and migration, and increased apoptosis and monocyte adhesion. The data matched with the downregulation of CDH13 in artery samples of atherosclerosis patients. The cellular phenotypes were also in line with our in vivo data of Cdh13 and Apoe double-KO (Cdh13-/-/Apoe-/-) mice, which showed increased aortic lesion areas when fed on a high-fat diet compared to Apoe-/- mice. Furthermore, prediction using TargetScan, miRWalk, and scanMiRApp databases identified the potential binding of several EC-expression microRNAs (mir) on 3’UTR of CDH13. Several disease-associated variants were mapped to the predicted binding sites of a few microRNAs, including mir-let7, mir-30, and mir-125. The dual luciferase-based RNA interference (RNAi) assay confirmed the binding of mir-let7 on 3’UTR of CDH13. Transcriptional activation of CDH13-AS2 by the enzymatically inactivated Cas9 (dCas9) system diminished the binding of mir-let7 and increased CDH13 expression. Conclusions At the CDH13 locus, CDH13 and CDH13-AS2 are two causal genes, whose downregulation likely contributes to CAD. CDH13-AS2 bound and stabilized CDH13 partially by preventing mir-let7 mediated degradation of CDH13 mRNA, suggesting therapeutic potentials.

Aortic Aneurysm with and without Dissection and Concomitant Atherosclerosis-Differences in a Retrospective Study.

Thoracic aortic aneurysm is a latent disease with a high risk of death. Today, as data are accumulating, an estimation of the differences in thoracic aneurysm in men and women of different age groups is required. The present study evaluated the type of atherosclerotic aortic lesions in males and females at different ages regarding the presence or absence of aortic dissection. A retrospective analysis of clinical and morphological data of 43 patients with thoracic aortic aneurysm was carried out. Patients were divided into groups based on the presence or absence of thoracic aneurysm dissection. Our results of a comparative analysis of the age of study participants showed that patients with aneurysm dissection were younger than patients without dissection. In the subgroup of patients with aortic dissection, the mean age was 50.6 years old, and in patients without aortic dissection, the mean age was 55.0 years old. When conducting a frequency analysis using Fisher's exact test, it was found that in men and women aneurysm dissection was not associated with atherosclerotic lesions of the aorta. In women and men, aneurysm dissection was not associated with stage of atherosclerotic lesions of the aorta regardless of age; no statistically significant differences were found between the groups with and without aneurysm dissection (p > 0.05). Dissection of the thoracic aneurysm developed in the absence of severe atherosclerosis of the thoracic aorta. Only 18.6% men and women possessed atherosclerotic plaques of types IV and V.

Unraveling aortic hemodynamics using fluid structure interaction: biomechanical insights into bicuspid aortic valve dynamics with multiple aortic lesions.

Aortic lesions, exemplified by bicuspid aortic valves (BAVs), can complicate congenital heart defects, particularly in Turner syndrome patients. The combination of BAV, dilated ascending aorta, and an elongated aortic arch presents complex hemodynamics, requiring detailed analysis for tailored treatment strategies. While current clinical decision-making relies on imaging modalities offering limited biomechanical insights, integrating high-performance computing and fluid-structure interaction algorithms with patient data enables comprehensive evaluation of diseased anatomy and planned intervention. In this study, a patient-specific workflow was utilized to biomechanically assess a Turner syndrome patient's BAV, dilated ascending aorta, and elongated arch. Results showed significant improvements in valve function (effective orifice area, EOA increased approximately twofold) and reduction in valve stress (~ 1.8-fold) following virtual commissurotomy, leading to enhanced flow dynamics and decreased viscous dissipation (~ twofold) particularly in the ascending aorta. However, increased viscous dissipation in the distal transverse aortic arch offset its local reduction in the AAo post-intervention, emphasizing the elongated arch's role in aortic hemodynamics. Our findings highlight the importance of comprehensive biomechanical evaluation and integrating patient-specific modeling with conventional imaging techniques for improved disease assessment, risk stratification, and treatment planning, ultimately enhancing patient outcomes.

A penetrating aortic ulcer rapidly evolving into aortic dissection in a patient presenting with respiratory tract infection to the emergency department: an acute aortic syndrome case report

BackgroundPenetrating aortic ulcers (PAU) are life-threatening conditions which derive from severely advanced atherosclerotic lesions of the aorta. The clinical course is unpredictable; thus clinical vigilance should be maintained. It is very challenging to separate PAU from co-existing AAS as predisposing factors and findings overlap.Case presentationCase of 58-year-old gentleman, who presented for atypical chest pain in the setting of respiratory tract infection. Computed Tomographic angiography (CTA) of the chest showed a large PAU and intramural hematoma which rapidly progressed into an acute aortic dissection in the emergency department. Close follow up with cardiac point of care ultrasound one hour later detected an intimal flap which was not initially present on CTA. Patient underwent surgical aortic graft replacement and had an uneventful in-hospital stay.DiscussionThis case underlines the importance of broadening differential diagnoses in atypical presentations in patients with risk factors. Prompt intervention and careful management are imperative to optimize patient outcomes and prevent complications of aortic lesions. Cardiac point of care ultrasound can help in detecting progression of dynamic atherosclerotic diseases such as acute aortic syndrome.

Editorial: Proven and innovative methods of ex vivo examination of atherosclerotic and aortic valve lesions

Editorial: Proven and innovative methods of ex vivo examination of atherosclerotic and aortic valve lesions

Overview and Future Direction of Embolic Stroke of Undetermined Source from the Insights of CHALLENGE ESUS/CS Registry.

Cryptogenic stroke (CS) accounts for approximately one-fourth of acute ischemic strokes, with most cases derived from embolic etiologies. In 2014, embolic stroke of undetermined source (ESUS) was advocated and the efficacy of anticoagulant therapy was anticipated. However, 3 large-scale clinical trials failed to demonstrate the superiority of direct oral anticoagulants (DOACs) over aspirin, potentially due to the heterogeneous and diverse pathologies of ESUS, including paroxysmal atrial fibrillation (AF), arteriogenic sources such as nonstenotic carotid plaque and aortic complicated lesion (ACL), patent foramen oval (PFO), and nonbacterial thrombotic endocarditis (NBTE) related to active cancer.Transesophageal echocardiography (TEE) is one of the most effective imaging modalities for assessing embolic sources in ESUS and CS. The Mechanisms of Embolic Stroke Clarified by Transesophageal Echocardiography for Embolic Stroke of Undetermined Source/Cryptogenic Stroke (CHALLENGE ESUS/CS) registry is a multicenter registry that enrolled consecutive patients with CS who underwent TEE at 8 hospitals in Japan between April 2014 and December 2016. Their mean age was 68.7±12.8 years, and 455 patients (67.2%) were male. The median National Institutes of Health Stroke Scale (NIHSS) score was 2. Since 7 analyses have been conducted from each institution to date, novel and significant insights regarding embolic origins and pathophysiologies of ESUS and CS were elucidated from this multicenter registry. This review discusses the diagnosis and treatment of ESUS and CS, tracing their past and future directions. Meaningful insights from the CHALLENGE ESUS/CS registry are also referenced and analyzed.

Ischemic Stroke in Adults With Congenital Heart Disease: Cumulative Incidence and Associated Factors.

When more patients with congenital heart disease reach adult age, increased incidence of long-term complications, including ischemic stroke, are expected. The aim of this study was to analyze cumulative incidence of ischemic stroke, associated factors, and case fatality in adult congenital heart disease. The study is based on Swedish national registers on congenital heart disease and stroke. Patients with congenital heart disease were followed between 2001 and 2018 for first-ever ischemic stroke events (ischemic stroke due to patent foramen ovale excluded). Factors possibly associated with ischemic stroke were analyzed using Cox regression models. Out of 8914 adult patients with congenital heart disease, 108 suffered ischemic stroke over a mean period of 7.6±4.7 years. The mean age at ischemic stroke was 53.8 years, and the cumulative incidence was 0.15% at 1 year, 0.5% at 5 years, and 1.5% at 10 years. In multivariable analysis, age (hazard ratio [HR], 1.04 [95% CI, 1.03-1.06]), diabetes (HR, 2.9 [95% CI, 1.3-6.4]), ejection fraction <50% (HR, 1.9 [95% CI, 1.1-3.4]), atrial septal defect (HR, 3.0 [95% CI, 1.03-8.5]), and aortic valve lesions (HR, 4.8 [95% CI, 1.6-14.1]) were associated with increased risk. Among those with ischemic stroke, approximately half were on antithrombotic treatment (anticoagulants or antiplatelets) before admission. Case fatality was 6.5%. The cumulative incidence of ischemic stroke was 1.5% after 10 years. In adult congenital heart disease, the type of heart lesion, diabetes, ejection fraction <50%, and age were important factors associated with ischemic stroke. Despite a relatively young age, mortality is a significant threat. At time of the ischemic stroke event, approximately half of the patients were on antithrombotic treatment.

Application of preset coronary artery orifice patch in Bentall surgery

BackgroundBentall surgery is the main method for treating aortic root lesions, but traditional Bentall method is very difficult for patients with mild aortic sinus dilation to directly anastomose the coronary artery orifice with graft.Case presentationA 41-year-old man was admitted to hospital after severe chest pain. Computed tomography angiography(CTA)revealed a type A aortic dissection. Echocardiography showed moderate aortic valve regurgitation and an aortic sinus diameter of 38 mm( mm). The patient underwent emergency Bentall surgery (using a preset coronary artery orifice patch), total arch replacement, and implantation of a graft into the descending aorta. Follow-up echocardiography showed the patient cardiac function was good, and there was no residual leakage at the coronary artery orifice.ConclusionsThis method is an alternative to traditional Bentall surgery and is suitable for all aortic root lesions, especially those with mild aortic sinus dilation or concomitant aortic dissection.

Tetrahydropalmatine promotes macrophage autophagy by inhibiting the AMPK/mTOR pathway to attenuate atherosclerosis.

Atherosclerosis (AS) is a chronic progressive arterial disease that is associated with macrophage autophagy and AMP-activated protein kinase (AMPK)/mechanistic target of the rapamycin (mTOR) pathway. Tetrahydropalmatine (THP) can activate AMPK-dependent autophagy. We aim to study the mechanism of macrophage autophagy mediated by THP in the treatment of AS via the AMPK/mTOR pathway. High-fat diet apolipoprotein E-deficient mice and ox-LDL-induced RAW264.7 cells were used to mimic the AS model, then THP was administered. Cell viability was detected by MTT. Pathological aorta lesions were detected using Hematoxylin and Eosin, Masson, and oil red staining. Lipid metabolism indices and inflammatory factors were measured using ELISA. A transmission electron microscope was used to observe autophagosomes. Autophagy and AMPK/mTOR pathway protein expression was detected by immunofluorescence and Western blot. The AMPK inhibitor 9-β-d-Arabinofuranosyl Adenine (Ara-A) was used to validate the effect of THP. The mRNA expression of Beclin-1 and MCP-1 was detected by q-PCR. THP administration regulated lipid metabolism by lowering total cholesterol, triacylglycerol, low-density lipoprotein, and high-density lipoprotein levels, and suppressed aortic damage. THP suppressed aortic damage and regulated lipid metabolism by altering serum lipid levels. THP reduced inflammation and macrophage CD68 expression. Twenty μg/mL THP reduced cell viability. THP decreased cholesterol uptake and increased efflux, promoting autophagy. THP increased autophagosome number, LC3B expression, and autophagy markers p-AMPK/AMPK and LC3-II/LC3-I. THP also decreased p-mTOR/mTOR and P62. THP increased Beclin-1 mRNA expression and decreased MCP-1 mRNA expression. Ara-A reversed THP's effects. THP promotes macrophage autophagy by inhibiting the AMPK/mTOR pathway to attenuate AS.

Highly sensitive magnetic particle imaging of abdominal aortic aneurysm NETosis with anti-Ly6G iron oxide nanoparticles

Abdominal aortic aneurysms (AAA) are a significant health concern in developed countries due to their considerable mortality rate. The crucial factor of the progression of AAA is the release of neutrophils and neutrophil extracellular traps (NETs). Magnetic particle imaging (MPI) is a new imaging technique that offers the capability to detect superparamagnetic iron oxide nanoparticles (SPION) with exceptional sensitivity. We aimed to investigate the functional imaging of MPI for the detection and monitoring of neutrophil infiltration within AAA. A novel multimodal imaging agent targeting neutrophils, PEG-Fe3O4-Ly6G–Cy7 nanoparticles (Ly6G NPs), were designed by coupling Fe3O4 nanoparticles with Ly6G antibodies and Cy7. The targeting and sensitivity of Ly6G NPs were assessed using MPI and fluorescence imaging (FLI) in the AAA mouse model. After the inhibition of NETosis, the degree of neutrophil infiltration and AAA severity were assessed using MPI with Ly6G NPs. Ly6G NPs accurately localized and quantitatively analyzed AAA lesion sites in mice using MPI/FLI/CT. Compared to the control group, elevated MPI and FLI signal intensities were detected at the abdominal aortic lesion site, and neutrophil infiltration and NETs accumulation were detected by histological analysis in the AAA models. After the inhibition of NETs accumulation in vivo, pathological damage in the abdominal aorta was significantly reduced, along with a decrease in the accumulation of Ly6G NPs and MPI signals. This multimodal MPI strategy revealed that nanoparticles targeting Ly6G can be used to detect neutrophil infiltration within AAA and monitor AAA severity.

Protective role of S-adenosylmethionine on high fat/high cholesterol diet-induced hepatic and aortic lesions and oxidative stress in guinea pigs.

S-adenosylmethionine (SAM) is the main methyl group donor and has antioxidant potential. In this study, preventive and regressive potential of SAM were investigated in high fat/high cholesterol (HFHC) diet-induced non-alcoholic fatty liver disease (NAFLD) in guinea pigs. They were injected with SAM (50 mg/kg, i.p.) for 6 weeks along with HFHC diet or 4 weeks after HFHC diet. Serum transaminase activities, total cholesterol (TC), triglyceride (TG), cytochrome p450-2E1 (CYP2E1) and hydroxyproline (Hyp) levels, prooxidative and antioxidative parameters, protein expressions of α-smooth muscle actin (α-SMA) and transforming growth factor-β1 (TGF-β1) together with histopathological changes were examined in the liver. SAM treatment diminished HFHC diet-induced increases in serum transaminase activities and hepatic TC, TG, CYP2E1, Hyp, α-SMA and TGF-β1 expressions and ameliorated prooxidant-antioxidant balance. Histopathological scores for hepatic steatosis, inflammation, and fibrosis were decreased by SAM treatment. Increases in TC, diene conjugate levels, and lipid vacuoles within the tunica media of the aorta were reduced in HFHC-fed animals treated with SAM. These protective effects were also detected in the regression period of HFHC-guinea pigs due to SAM. In conclusion, SAM treatment was found to be effective in prevention and regression of HFHC-induced hepatic and aortic lesions together with decreases in oxidative stress in guinea pigs with NAFLD.

TRIM25 activates Wnt/β-catenin signalling by destabilising MAT2A mRNA to drive thoracic aortic aneurysm development.

This study explored the roles of methionine adenosyltransferase 2A (MAT2A) and tripartite motif containing 25 (TRIM25) in the progression of thoracic aortic aneurysm (TAA). The TAA model was established based on the β-aminopropionitrile method. The effects of MAT2A on thoracic aortic lesions and molecular levels were analyzed by several pathological staining assays (hematoxylin-eosin, Verhoeff-Van Gieson, TUNEL) and molecular biology experiments (qRT-PCR, Western blot). Angiotensin II (Ang-II) was used to induce injury in vascular smooth muscle cells (VSMCs) in vitro. The effects of MAT2A, shMAT2A, shTRIM25 and/or Wnt inhibitor (IWR-1) on the viability, apoptosis and protein expressions of VSMCs were examined by CCK-8, Annexin V-FITC/PI and Western blot assays. In TAA mice, overexpression of MAT2A alleviated thoracic aortic injury, inhibited the aberrant expressions of aortic contractile proteins and dedifferentiation markers, and blocked the activation of Wnt/β-catenin pathway. In Ang-II-induced VSMCs, up-regulation of MAT2A increased cellular activity and repressed the expression of β-catenin protein. TRIM25 knockdown promoted activity of VSMCs, inhibited apoptosis, and blocked the Wnt/β-catenin pathway activation by binding to MAT2A. IWR-1 partially counteracted the regulatory effects of shMAT2A. Collectively, TRIM25 destabilises the mRNA of MAT2A to activate Wnt/β-catenin signaling and ultimately exacerbate TAA injury.

Lack of alpha CGRP exacerbates the development of atherosclerosis in ApoE-knockout mice

The effects of calcitonin gene-related peptide (CGRP) on atherosclerosis remain unclear. We used apolipoprotein E-deficient (ApoE−/−) mice to generate double-knockout ApoE−/−:CGRP−/− mice lacking alpha CGRP. ApoE−/−:CGRP−/− mice exhibited larger atherosclerotic plaque areas, peritoneal macrophages with enhanced migration functions, and elevated levels of the inflammatory cytokine tumor necrosis factor (TNF)-⍺. Thus, we also explored whether inhibiting TNF-⍺ could improve atherosclerosis in ApoE−/−:CGRP−/− mice by administering etanercept intraperitoneally once a week (5 mg/kg) alongside a high-fat diet for 2 weeks. This treatment led to significant reductions in aortic root lesion size, atherosclerotic plaque area and macrophage migration in ApoE−/−:CGRP−/− mice compared with mice treated with human IgG (5 mg/kg). We further examined whether results observed in ApoE−/−:CGRP−/− mice could similarly be obtained by administering a humanized monoclonal CGRP antibody, galcanezumab, to ApoE−/− mice. ApoE−/− mice were subcutaneously administered galcanezumab at an initial dose of 50 mg/kg, followed by a dose of 30 mg/kg in the second week. Galcanezumab administration did not affect systolic blood pressure, serum lipid levels, or macrophage migration but led to a significant increase in lipid deposition at the aortic root. These findings suggest that alpha CGRP plays a critical role in inhibiting the progression of atherosclerosis.

Factors Affecting Compression of the Left Subclavian Artery Bridging Stent In Zone 2 Fenestrated Endovascular Arch Repair.

Left subclavian artery (LSA) preservation during thoracic endovascular aortic repair (TEVAR) has been related to low morbidity. This study investigated the incidence of LSA stent compression in patients managed with fenestrated endovascular arch repair (f-Arch) and evaluated the impact of anatomic and technical factors on LSA stent outcomes. A single-center retrospective analysis of patients managed with single-fenestration devices (Cook Medical, Bloomington, IN, USA) for LSA preservation, between January 1, 2012 and November 30, 2023, was conducted. Anatomic (arch type, bovine arch, distance between the LSA and most proximal bone structure, left common carotid artery and aortic lesion, take-off angle, diameter, thrombus, calcification, dissection, tortuosity) and technical parameters (stent type, diameter, length, relining, post-dilation) were evaluated. Stent compression was any ≥50% stenosis (using center luminal line) of the stent compared with its initial diameter. Clinical outcomes included stroke and upper limb ischemia at 30 days and follow-up. Technical outcomes included stent compression and need for reintervention. Fifty-four cases were included. Only balloon-expandable covered stents were used, and relining during the index procedure was performed in 18%. No stroke or arm ischemia was recorded. One stent compression was detected at 30 days. During follow-up, no stroke or arm ischemia was diagnosed. Nine cases (18%) presented stent compression, with a mean time of stent-compression diagnosis at 18 months (interquartile range [IQR]=37, range=1-58 months) after the index procedure. Five (56%) underwent secondary relining. Follow-up after reintervention was uneventful. Lower distance to the nearest bone structure (compression group [CG]: 11.7±8.9 mm vs non-compression group [NCG]: 23.0±7.8 mm, p=0.003) and higher tortuosity index (CG: 1.3±0.4 vs NCG: 1.2±0.1, p=0.03) were associated with LSA stent compression. LSA stent compression in patients managed with f-Arch affected 1 in 5 cases, without clinical consequences. Distance to the nearest bone structure and higher tortuosity were associated with LSA stent compression. Fenestrated endovascular arch repair for the preservation of the left subclavian artery (LSA) in patients needing landing within the aortic arch has been performed with encouraging outcomes. This analysis showed that LSA stent compression is met in 18% of patients, without though any clinical consequence. Pre-operative anatomic parameters, as lower distance to the nearest bone structure and higher tortuosity index affect negatively LSA stent performance while stent parameters seem to have no impact.