Administration of an antibody against apoptosis inhibitor of macrophage prevents aortic aneurysm progression in mice.

Apoptosis inhibitor of macrophage (AIM) is known to induce apoptosis resistance in macrophages and to exacerbate chronic inflammation, leading to arteriosclerosis. The role of AIM in aortic aneurysm (AA) remains unknown. This study examined the effects of an anti-AIM antibody in preventing AA formation and progression. In apolipoprotein E-deficient mice, AA was induced by subcutaneous angiotensin II infusion. Mice were randomly divided into two groups: (i) AIM group; weekly anti-murine AIM monoclonal antibody injection (n = 10), and (ii) IgG group; anti-murine IgG antibody injection as control (n = 14). The AIM group, compared with the IgG group, exhibited reduced AA enlargement (aortic diameter at 4 weeks: 2.1 vs. 2.7 mm, respectively, p = 0.012); decreased loss of elastic lamellae construction; reduced expression levels of IL-6, TNF-α, and MCP-1; decreased numbers of AIM-positive cells and inflammatory M1 macrophages (AIM: 1.4 vs. 8.0%, respectively, p = 0.004; M1 macrophages: 24.5 vs. 55.7%, respectively, p = 0.017); and higher expression of caspase-3 in the aortic wall (22.8 vs. 10.5%, respectively, p = 0.019). Our results suggest that administration of an anti-AIM antibody mitigated AA progression by alleviating inflammation and promoting M1 macrophage apoptosis.

Medical treatments for abdominal aortic aneurysm: an overview of clinical trials.

INTRODUCTION: Abdominal aortic aneurysm is a progressive, segmental, abdominal aortic dilation associated with a high mortality rate. Abdominal aortic aneurysms with diameters larger than 55 mm are associated with a high risk of rupture, and the most effective treatment options are surgical repair. Close observation and lifestyle adjustments are recommended for smaller abdominal aortic aneurysms with lower rupture risk. The development of medical therapies that limit or prevent the progression, expansion, and eventual rupture of abdominal aortic aneurysms remains an unmet clinical need. AREAS COVERED: This review provides an overview of completed and ongoing clinical trials examining the efficacies of various drug classes, including antibiotics, antihypertensive drugs, hypolipidemic drugs, hypoglycemic drugs, and other potential therapies for abdominal aortic aneurysms. A search of PubMed, Web of Science, Clinical Trials, and another six clinical trial registries was conducted in January 2024. EXPERT OPINION: None of the drugs have enough evidence to indicate that they can effectively inhibit the dilation of abdominal aortic aneurysm. More clinical trial data is required to support the efficacy of propranolol. Future research should also explore different drug delivery mechanisms, such as nanoparticles, to elevate drug concentration at the aneurysm wall.

Artificial intelligence-driven multiomics predictive model for abdominal aortic aneurysm subtypes to identify heterogeneous immune cell infiltration and predict disease progression.

BACKGROUND: Abdominal aortic aneurysm (AAA) poses a significant health risk and is influenced by various compositional features. This study aimed to develop an artificial intelligence-driven multiomics predictive model for AAA subtypes to identify heterogeneous immune cell infiltration and predict disease progression. Additionally, we investigated neutrophil heterogeneity in patients with different AAA subtypes to elucidate the relationship between the immune microenvironment and AAA pathogenesis. METHODS: This study enrolled 517 patients with AAA, who were clustered using k-means algorithm to identify AAA subtypes and stratify the risk. We utilized residual convolutional neural network 200 to annotate and extract contrast-enhanced computed tomography angiography images of AAA. A precise predictive model for AAA subtypes was established using clinical, imaging, and immunological data. We performed a comparative analysis of neutrophil levels in the different subgroups and immune cell infiltration analysis to explore the associations between neutrophil levels and AAA. Quantitative polymerase chain reaction, Western blotting, and enzyme-linked immunosorbent assay were performed to elucidate the interplay between CXCL1, neutrophil activation, and the nuclear factor (NF)-κB pathway in AAA pathogenesis. Furthermore, the effect of CXCL1 silencing with small interfering RNA was investigated. RESULTS: Two distinct AAA subtypes were identified, one clinically more severe and more likely to require surgical intervention. The CNN effectively detected AAA-associated lesion regions on computed tomography angiography, and the predictive model demonstrated excellent ability to discriminate between patients with the two identified AAA subtypes (area under the curve, 0.927). Neutrophil activation, AAA pathology, CXCL1 expression, and the NF-κB pathway were significantly correlated. CXCL1, NF-κB, IL-1ß, and IL-8 were upregulated in AAA. CXCL1 silencing downregulated NF-κB, interleukin-1ß, and interleukin-8. CONCLUSION: The predictive model for AAA subtypes demonstrated accurate and reliable risk stratification and clinical management. CXCL1 overexpression activated neutrophils through the NF-κB pathway, contributing to AAA development. This pathway may, therefore, be a therapeutic target in AAA.

The Use of Pressure Recording Analytical Method in Patients Undergoing Endovascular Repair for Abdominal Aortic Aneurysm: The Impact on Clinical Decisions for the Appropriate Postoperative Setting and Cost-effective Analysis.

OBJECTIVE: To analyze the use of the Pressure Recording Analytical Method (PRAM), an hemodynamic monitoring system, in evaluating intraoperative and postoperative hemodynamic instability in patients undergoing endovascular repair for abdominal aortic aneurysm, and to evaluate if the decision to refer patients to a ordinary ward or to a Cardiac Step-Down Unit (CSDU) after the intervention on the basis of intraoperative hemodynamic monitoring could be more cost-effective. MATERIALS AND METHODS: After preoperative clinical evaluation, 44 patients were divided in this non-randomised study into two groups according to their postoperative destination: Group 1-ward (N=22) and Group 2-CSDU (N=22). All patients underwent monitoring with PRAM during the intervention and in the 24 postoperative hours, measuring several indices of myocardial contractility and other hemodynamic variables. RESULTS: According to the variability of two parameters, Stroke Volume Variation and Pulse Pressure Variation, patients were classified as stable or unstable. Unstable patients showed a significant alteration in several hemodynamic indices, in comparison to stable ones. According to the intraoperative monitoring, eight high risk patients could have been sent to an ordinary ward due to their stability, with a reduction in the improper use of CSDU and, consequently, in costs. CONCLUSIONS: Hemodynamic monitoring with PRAM can be useful in these patients, both for intraoperative management and for the choice of the more appropriate postoperative setting, possibly reducing the improper use of CSDU for hemodynamically stable patients who are judged to be at high risk preoperatively, and re-evaluating low surgical risk patients with an unstable intraoperative pattern, with a possible reduction in costs.

ERRATUM: Genetic testing for inherited cardiovascular diseases. A position statement of the Polish Cardiac Society endorsed by Polish Society of Human Genetics and Cardiovascular Patient Communities.

According to the latest guidelines of European and American medical societies, genetic testing (GT) is essential in cardiovascular diseases for establishing diagnosis, predicting prognosis, enabling initiation of disease-modifying therapy, and preventing sudden cardiac death. The GT result may be relevant for cascade GT in the patient's relatives, for planning his/her profession and physical activity, and for procreative counseling. This position statement has been prepared due to the scarcity of GT in cardiovascular diseases in Poland and the need to expand its availability. We give a concise description of the genetic background of cardiomyopathies, channelopathies, aortopathies, familial hypercholesterolemia, pheochromocytomas, and paragangliomas. The article discusses various aspects of GT in specific populations, such as children or athletes, and also presents prenatal genetic diagnostics. We propose recommendations for GT and counselling, which take into account Polish needs and capabilities. We give an outline of legal regulations, good clinical practice in GT with respect for patient rights, the role of cardiologists and clinical geneticists in GT planning and post-test counseling, and the requirements for laboratories performing genetic tests. The Polish Cardiac Society and Polish Society of Human Genetics experts speak with one voice with cardiovascular patient communities to underline the need for a law on GT and increasing the availability of GT for cardiovascular patients.

Aorto-uni-iliac stent grafts without crossover fem-fem bypass for treatment of abdominal aortic aneurysms: A report of two cases.

INTRODUCTION AND IMPORTANCE: Arterial aneurysm is a serious condition caused by weakened arterial walls. Aorto-uni-iliac (AUI) and femorofemoral bypass are safe and effective options for managing abdominal aortic aneurysm (AAA). However, fem-fem bypass leads to longer surgical procedures and introduces additional risks such as graft infection, occlusion, wound complications, and peripheral vascular problems. This report highlights two successful cases of AAA management using the AUI approach without the need for fem-fem bypass. CASE PRESENTATION: Two male patients, both aged about 70, presented at our medical facility complaining of abdominal pain. Investigations unveiled an approximately 10-cm AAA that was previously undetected. Subsequently, we performed an elective AUI procedure without fem-fem bypass, marking the first instance of this technique being employed in Iran successfully. CLINICAL DISCUSSION: The placement of an AUI stent graft is generally less technically demanding compared to that of a standard bifurcated graft, especially when anatomical constraints are severe, making the latter difficult or even impossible to deploy. Beside the longer duration of stent deployment, sometimes we encounter contralateral complications to cannulate the main body. The AUI is typically used in emergency situations or when the distal aorta's internal diameter is small. The femoral-femoral bypass is advised in nearly all circumstances. CONCLUSION: AUI stent grafts are still a viable option for treatments of AAA, especially in cases of severe aortoiliac occlusive disease or comorbidities. AUI without crossover bypass is a viable option in the patients who have stenosis of contralateral iliac artery.

A rare case of giant left sinus of Valsalva aneurysm complicated by thrombus formation.

A rare transthoracic echocardiographic image of left sinus of Valsalva aneurysm complicated by thrombus formation.

Site-specific genetic and functional signatures of aortic endothelial cells at aneurysm predilection sites in healthy and AngII ApoE-/- mice.

Aortic aneurysm is characterized by a pathological dilation at specific predilection sites of the vessel and potentially results in life-threatening vascular rupture. Herein, we established a modified "Häutchen method" for the local isolation of endothelial cells (ECs) from mouse aorta to analyze their spatial heterogeneity and potential role in site-specific disease development. When we compared ECs from aneurysm predilection sites of healthy mice with adjacent control segments we found regulation of genes related to extracellular matrix remodeling, angiogenesis and inflammation, all pathways playing a critical role in aneurysm development. We also detected enhanced cortical stiffness of the endothelium at these sites. Gene expression of ECs from aneurysms of the AngII ApoE-/- model when compared to sham animals mimicked expression patterns from predilection sites of healthy animals. Thus, this work highlights a striking genetic and functional regional heterogeneity in aortic ECs of healthy mice, which defines the location of aortic aneurysm formation in disease.

Inflammatory Markers and Aortic Aneurysms: Exploring the Role of Hs-CRP and MHR in Ascending Aortic Aneurysm Development.

Background: Aortic aneurysms, particularly those affecting the ascending aorta, pose significant health risks due to their potential to cause life-threatening complications such as rupture and dissection. While the etiology of ascending aortic aneurysms has traditionally been associated with non-inflammatory processes, emerging evidence suggests a potential role of inflammation in their development. Methods: This study investigates the relationship between inflammatory markers and ascending aortic aneurysms, focusing on high-sensitivity C-reactive protein (hs-CRP) and the monocyte-to-HDL ratio (MHR). A total of 135 patients with ascending aortic aneurysms and 40 control subjects underwent comprehensive evaluations, including echocardiography, computed tomography imaging, and serum biomarker measurements. Results: The results indicate significantly elevated levels of hs-CRP and MHR in patients with ascending aortic aneurysms compared to the control group, suggesting a potential inflammatory component in the pathogenesis of these aneurysms. However, the precise mechanisms underlying this association remain to be elucidated. Conclusion: Despite limitations such as the cross-sectional study design and relatively small sample size, this study provides valuable insights into the potential involvement of inflammation in ascending aortic aneurysms. Further research, including longitudinal studies and histopathological analysis of aortic tissue, is warranted to confirm these findings and explore the utility of inflammatory markers as diagnostic and prognostic indicators in this patient population.

Low-profile versus standard-profile stent grafts in the treatment of abdominal aortic aneurysm: a case-matched study.

Introduction: Endovascular aortic repair (EVAR) is nowadays a widespread method of managing abdominal aortic aneurysm (AAA). Low-profile stent grafts (LPSGs) enable treatment of patients with complex and anatomically challenging aneurysms, and facilitate a percutaneous and thus less invasive procedure. Aim: To assess the outcomes of EVAR with low-profile versus standard-profile stent grafts (SPSGs). Material and methods: Thirty-one patients with abdominal aortic aneurysms (AAA) were treated by endovascular aortic repair (EVAR) using LPSGs. The control group of patients treated with SPSGs was matched with MedCalc software. The clinical records and the preoperative and follow-up computed tomography angiography of patients who underwent endovascular treatment of AAA were included in this study. Results: Patients in the LPSG group had significantly more often low access vessel diameter (< 6 mm) compared to the SPSG group (38.7% vs. 6.7%, p = 0.003). In 1-year follow-up, there was no rupture, no infection, no conversion to open repair and no aneurysm-related death. Five secondary interventions were necessary in the SPSG group and only 1 in the LPSG group (p = 0.09). Type of stent graft was not a risk factor of perioperative complications, presence of endoleak or reintervention (p > 0.05). Risk factors for perioperative complications were COPD and conical neck (OR = 6.3, 95% CI: 1.5-25, p = 0.01 and OR = 6.2, 95% CI: 1-39.76, p = 0.04). The risk factor for endoleak was lower maximal aneurysm diameter. The risk factor for reintervention was proximal neck diameter (OR = 0.77, 95% CI: 0.-0.97, p = 0.03). Conclusions: Our study showed that use of LPSGs is a safe and viable method for patients with narrow access vessels who are not eligible for standard-profile systems.

Early and Late Aortic-Related Mortality and Rupture After Fenestrated-Branched Endovascular Aortic Repair of Thoracoabdominal Aortic Aneurysms: A Prospective Multicenter Cohort Study.

BACKGROUND: Fenestrated-branched endovascular aortic repair (FB-EVAR) has been used as a minimally invasive alternative to open surgical repair to treat patients with thoracoabdominal aortic aneurysms (TAAAs). The aim of this study was to evaluate aortic-related mortality (ARM) and aortic aneurysm rupture after FB-EVAR of TAAAs. METHODS: Patients enrolled in 8 prospective, nonrandomized, physician-sponsored investigational device exemption studies between 2005 and 2020 who underwent elective FB-EVAR of asymptomatic intact TAAAs were analyzed. Primary end points were ARM, defined as any early mortality (30 days or in hospital) or late mortality from aortic rupture, dissection, organ or limb malperfusion attributable to aortic disease, complications of reinterventions, or aortic rupture. Secondary end points were early major adverse events, TAAA life-altering events (defined as death, permanent spinal cord injury, permanent dialysis, or stroke), all-cause mortality, and secondary interventions. RESULTS: A total of 1109 patients were analyzed; 589 (53.1%) had extent I-III and 520 (46.9%) had extent IV TAAAs. Median age was 73.4 years (interquartile range, 68.1-78.3 years); 368 (33.2%) were women. Early mortality was 2.7% (n=30); congestive heart failure was associated with early mortality (odds ratio, 3.30 [95% CI, 1.22-8.02]; P=0.01). Incidence of early aortic rupture was 0.4% (n=4). Incidence of early major adverse events and TAAA life-altering events was 20.4% (n=226) and 7.7% (n=85), respectively. There were 30 late ARMs; 5-year cumulative incidence was 3.8% (95% CI, 2.6%-5.4%); older age and extent I-III TAAAs were independently associated with late ARM (each P<0.05). Fourteen late aortic ruptures occurred; 5-year cumulative incidence was 2.7% (95% CI, 1.2%-4.3%); extent I-III TAAAs were associated with late aortic rupture (hazard ratio, 5.85 [95% CI, 1.31-26.2]; P=0.02). Five-year all-cause mortality was 45.7% (95% CI, 41.7%-49.4%). Five-year cumulative incidence of secondary intervention was 40.3% (95% CI, 35.8%-44.5%). CONCLUSIONS: ARM and aortic rupture are uncommon after elective FB-EVAR of asymptomatic intact TAAAs. Half of the ARMs occurred early, and most of the late deaths were not aortic related. Late all-cause mortality rate and the need for secondary interventions were 46% and 40%, respectively, 5 years after FB-EVAR. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT02089607, NCT02050113, NCT02266719, NCT02323581, NCT00583817, NCT01654133, NCT00483249, NCT02043691, and NCT01874197.

Single-cell RNA sequencing reveals that NRF2 regulates vascular smooth muscle cell phenotypic switching in abdominal aortic aneurysm.

Abdominal aortic aneurysm (AAA) is a life-threatening disease characterized by extensive membrane destruction in the vascular wall that is closely associated with vascular smooth muscle cell (VSMC) phenotypic switching. A thorough understanding of the changes in regulatory factors during VSMC phenotypic switching is essential for managing AAA therapy. In this study, we revealed the impact of NRF2 on the modulation of VSMC phenotype and the development of AAA based on single-cell RNA sequencing analysis. By utilizing a murine model of VSMC-specific knockout of nuclear factor E2-related factor 2 (NRF2), we observed that the absence of NRF2 in VSMCs exacerbated AAA formation in an angiotensin II-induced AAA model. The downregulation of NRF2 promoted VSMC phenotypic switching, leading to an enhanced inflammatory response. Through genome-wide transcriptome analysis and loss- or gain-of-function experiments, we discovered that NRF2 upregulated the expression of VSMC contractile phenotype-specific genes by facilitating microRNA-145 (miR-145) expression. Our data identified NRF2 as a novel regulator involved in maintaining the VSMC contractile phenotype while also influencing AAA formation through an miR-145-dependent regulatory mechanism.

Contributions of Germline and Somatic Mosaic Genetics to Thoracic Aortic Aneurysms in Nonsyndromic Individuals.

BACKGROUND: Thoracic aortic aneurysm (TAA) is associated with significant morbidity and mortality. Although individuals with family histories of TAA often undergo clinical molecular genetic testing, adults with nonsyndromic TAA are not typically evaluated for genetic causes. We sought to understand the genetic contribution of both germline and somatic mosaic variants in a cohort of adult individuals with nonsyndromic TAA at a single center. METHODS AND RESULTS: One hundred eighty-one consecutive patients <60 years who presented with nonsyndromic TAA at the Massachusetts General Hospital underwent deep (>500×) targeted sequencing across 114 candidate genes associated with TAA and its related functional pathways. Samples from 354 age- and sex-matched individuals without TAA were also sequenced, with a 2:1 matching. We found significant enrichments for germline (odds ratio [OR], 2.44, P=4.6×10-6 [95% CI, 1.67-3.58]) and also somatic mosaic variants (OR, 4.71, P=0.026 [95% CI, 1.20-18.43]) between individuals with and without TAA. Likely genetic causes were present in 24% with nonsyndromic TAA, of which 21% arose from germline variants and 3% from somatic mosaic alleles. The 3 most frequently mutated genes in our cohort were FLNA (encoding Filamin A), NOTCH3 (encoding Notch receptor 3), and FBN1 (encoding Fibrillin-1). There was increased frequency of both missense and loss of function variants in TAA individuals. CONCLUSIONS: Likely contributory dominant acting genetic variants were found in almost one quarter of nonsyndromic adults with TAA. Our findings suggest a more extensive genetic architecture to TAA than expected and that genetic testing may improve the care and clinical management of adults with nonsyndromic TAA.

Innovation in pathogenesis and management of aortic aneurysm.

Aortic aneurysm (AA) refers to the persistent dilatation of the aorta, exceeding three centimeters. Investigating the pathophysiology of this condition is important for its prevention and management, given its responsibility for more than 25000 deaths in the United States. AAs are classified based on their location or morphology. various pathophysiologic pathways including inflammation, the immune system and atherosclerosis have been implicated in its development. Inflammatory markers such as transforming growth factor ß, interleukin-1ß, tumor necrosis factor-α, matrix metalloproteinase-2 and many more may contribute to this phenomenon. Several genetic disorders such as Marfan syndrome, Ehler-Danlos syndrome and Loeys-Dietz syndrome have also been associated with this disease. Recent years has seen the investigation of novel management of AA, exploring the implication of different immune suppressors, the role of radiation in shrinkage and prevention, as well as minimally invasive and newly hypothesized surgical methods. In this narrative review, we aim to present the new contributing factors involved in pathophysiology of AA. We also highlighted the novel management methods that have demonstrated promising benefits in clinical outcomes of the AA.

A prospective longitudinal study of risk factors for abdominal aortic aneurysm.

The aim of this study was to identify risk factors for abdominal aortic aneurysm (AAA) from the largest Welsh screening cohort to date. Patients were recruited from 1993 (to 2015) as part of the South East Wales AAA screening programme through general practitioners. Demographic data and risk factors were collected by means of a self-report questionnaire. Statistical tests were performed to determine whether associations could be observed between AAA and potential risk factors. Odds ratios (OR) were also calculated for each of the risk factors identified. A total of 6879 patients were included in the study. Two hundred and seventy-five patients (4.0%) presented with AAA, of which 16% were female and 84% were male. Patients with AAA were older than the (no AAA) control group (p < 0.0001). The following risk factors were identified for AAA: family history of AAA (p < 0.0001); history of vascular surgery (p < 0.0001), cerebrovascular accident (p < 0.0001), coronary heart disease (p < 0.0001), diabetes (p < 0.0001), medication (p = 0.0018), claudication (p < 0.0001), smoking history (p = 0.0001) and chronic obstructive pulmonary disorder (p = 0.0007). AAA is associated with classical vascular risk factors, in addition to other less-well-documented risk factors including previous vascular surgery. These findings have practical implications with the potential to improve future clinical screening of patients in order to reduce AAA mortality.

Acute global testicular infarction: A rare and important complication after endovascular abdominal aortic aneurysm repair.

Testicular ischemia is one of the most rarely reported complications of endovascular abdominal aortic aneurysm repair (EVAR). Although the pathogenesis remains unclear, thromboembolic events in the setting of testicular artery origin occlusion by the stent graft and poor baseline collateral testicular circulation are presumed causes. A 73-year-old man developed acute right testicular infarction 3 days after EVAR, requiring orchiectomy. This case emphasizes the importance of recognizing and evaluating testicular pain after EVAR and counseling patients on this possible EVAR complication.

Dual-Drug Nanomedicine Assembly with Synergistic Anti-Aneurysmal Effects via Inflammation Suppression and Extracellular Matrix Stabilization.

Abdominal aortic aneurysm (AAA) represents a critical cardiovascular condition characterized by localized dilation of the abdominal aorta, carrying a significant risk of rupture and mortality. Current treatment options are limited, necessitating novel therapeutic approaches. This study investigates the potential of a pioneering nanodrug delivery system, RAP@PFB, in mitigating AAA progression. RAP@PFB integrates pentagalloyl glucose (PGG) and rapamycin (RAP) within a metal-organic-framework (MOF) structure through a facile assembly process, ensuring remarkable drug loading capacity and colloidal stability. The synergistic effects of PGG, a polyphenolic antioxidant, and RAP, an mTOR inhibitor, collectively regulate key players in AAA pathogenesis, such as macrophages and smooth muscle cells (SMCs). In macrophages, RAP@PFB efficiently scavenges various free radicals, suppresses inflammation, and promotes M1-to-M2 phenotype repolarization. In SMCs, it inhibits apoptosis and calcification, thereby stabilizing the extracellular matrix and reducing the risk of AAA rupture. Administered intravenously, RAP@PFB exhibits effective accumulation at the AAA site, demonstrating robust efficacy in reducing AAA progression through multiple mechanisms. Moreover, RAP@PFB demonstrates favorable biosafety profiles, supporting its potential translation into clinical applications for AAA therapy.

Diaphragmatic Hernia With Secondary Pneumothorax Due to Intestinal Perforation After Thoracoabdominal Aortic Aneurysm Operation: A Case Report.

A male in his 70s with a history of artificial vessel replacement for a thoracoabdominal aneurysm had been treated non-operatively for adhesive bowel obstruction during the past two months. The initial symptom was nausea and the patient was transferred to our hospital because of diffuse abdominal pain. Computed tomography revealed pneumothorax, diaphragmatic hernia, and bowel perforation. A left thoracic drain was inserted and air and clear yellow fluid were drained. Secondary pneumothorax was presumably caused by intestinal perforation associated with diaphragmatic hernia. Although reported cases with secondary pneumothorax associated with diaphragmatic hernia and intestinal perforation are caused by trauma, this complication can occur postoperatively.