The Relationship Between Serum Interleukin-1α and Asymptomatic Infrarenal Abdominal Aortic Aneurysm Size, Morphology, and Growth Rates.

OBJECTIVE/BACKGROUND: In a pilot study, a relationship between abdominal aortic aneurysm (AAA) diameter and serum interleukin (IL)-1α levels was reported, and that endothelial cell (EC) activation in vitro in response to serum from patients with AAA was blocked by anti-IL-1α antibodies. The aim of the present study was to further investigate the relationship between serum IL-1α and asymptomatic infrarenal AAA size, morphology, and growth rates. METHODS: Serum IL-1α was measured using enzyme linked immunosorbent assay in 101 patients with asymptomatic, infrarenal AAA and related to aneurysm size, morphology, and growth rates. RESULTS: IL-1α was measured in 101 patients. There was no statistically significant difference in mean age between men and women. IL-1α was detectable in 62.4% of patients; median IL-1α titre was 3.26 pg/mL. There was no statistically significant relationship between IL-1α and maximum AAA antero-posterior diameter as measured by ultrasound (p = .649), AAA morphology (aortic length [p = .394], sac [p = .369], and thrombus volume [p = .629]) as measured on computed tomography, absolute increase in AAA diameter (p = .214), or AAA growth rate (p = .230). CONCLUSION: IL-1α is detectable in the majority of patients with infrarenal AAA, but the cause and clinical significance of this novel observation remains unknown.

A case report of primary aortoduodenal fistula: A forgotten cause of gastrointestinal bleeding.

Aortoenteric fistula is one of the uncommon emergencies and is challenging to navigate for diagnostic testing. Here, we present a clinical case of an aortoduodenal fistula with primary etiology. A 73-year-old female patient with a history of hypertension was admitted to the hospital because of a 1-day history of melena. Ultrasound showed an abdominal aortic aneurysm sized (33 × 46) mm and a hematoma on the wall of the aorta. The patient underwent a gastrointestinal endoscopy with no bleeding point detected. However, the patient suddenly fell into a hemorrhagic shock on day 3 of admission. We rapidly performed fluid resuscitation, blood transfusion, a second gastrointestinal endoscopy, and a computed tomography scan of the abdomen with contrast injection that revealed a fistula from the abdominal aorta into the second segment of the duodenum. The patient was indicated for urgent endovascular aortic repair. Although this technique was successful with 3 abdominal aortic stents, the patient died due to multiorgan failure. Delayed diagnosis is the root cause of primary aortoduodenal fistula treatment failure, so it is important for clinicians to keep aortoduodenal fistula in mind as a possible cause of gastrointestinal bleeding in any patient.

TCF7L1 Accelerates Smooth Muscle Cell Phenotypic Switching and Aggravates Abdominal Aortic Aneurysms.

Phenotypic switching of vascular smooth muscle cells is a central process in abdominal aortic aneurysm (AAA) pathology. We found that knockdown TCF7L1 (transcription factor 7-like 1), a member of the TCF/LEF (T cell factor/lymphoid enhancer factor) family of transcription factors, inhibits vascular smooth muscle cell differentiation. This study hints at potential interventions to maintain a normal, differentiated smooth muscle cell state, thereby eliminating the pathogenesis of AAA. In addition, our study provides insights into the potential use of TCF7L1 as a biomarker for AAA.

Key ferroptosis-related genes in abdominal aortic aneurysm formation and rupture as determined by combining bioinformatics techniques.

Objectives: Abdominal aortic aneurysm (AAA) is a cardiovascular disease with high mortality and pathogenesis closely related to various cell death types, e.g., autophagy, apoptosis and pyroptosis. However, the association between AAA and ferroptosis is unknown. Methods: GSE57691 and GSE98278 dataset were obtained from the Gene Expression Omnibus database, and a ferroptosis-related gene (FRG) set was downloaded from the FerrDb database. These data were normalized, and ferroptosis-related differentially expressed genes (FDEGs, AAA vs. normal samples) were identified using the limma package in R. FRGs expression was analyzed by Gene Set Expression Analysis (GSEA), and FDEGs were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes (KEGG) pathway enrichment analyses using the clusterProfiler package in R and ClueGO in Cytoscape. Protein-protein interaction networks were assembled using Cytoscape, and crucial FDEGs were identified using CytoHubba. Critical FDEG transcription factors (TFs) were predicted with iRegulon. FDEGs were verified in GSE98278 set, and key FDEGs in AAA (compared with normal samples) and ruptured AAA (RAAA; compared with AAA samples) were identified. Ferroptosis-related immune cell infiltration and correlations with key genes were analyzed by CIBERSORT. Key FEDGs were reverified in Ang II-induced AAA models of ApoE-/- and CD57B/6J mice by immunofluorescence assay. Results: In AAA and normal samples, 40 FDEGs were identified, and the expression of suppressive FRGs was significantly downregulated with GSEA. For FDEGs, the GO terms were response to oxidative stress and cellular response to external stimulus, and the KEGG pathways were the TNF and NOD-like receptor signaling pathways. IL6, ALB, CAV1, PTGS2, NOX4, PRDX6, GPX4, HSPA5, HSPB1, and NCF2 were the most enriched genes in the crucial gene cluster. CEBPG, NFAT5, SOX10, GTF2IRD1, STAT1, and RELA were potential TFs affecting these crucial genes. Ferroptosis-related immune cells involved in AAA formation were CD8+ T, naive CD4+ T, and regulatory T cells (Tregs); M0 and M2 macrophages; and eosinophils. Tregs were also involved in RAAA. GPX4, SLC2A1, and PEBP1 expression was downregulated in both the RAAA and AAA samples. GPX4 and PEBP1 were more important in AAA because they influenced ferroptosis-related immune cell infiltration, and SLC2A1 was more important in RAAA. Conclusions: This is the first study to show that ferroptosis is crucial to AAA/RAAA formation. The TNF and NOD-like signaling pathways and ferroptosis-related immune cell infiltration play key roles in AAA/RAAA. GPX4 is a key ferroptosis-related gene in AAA. Ferroptosis and related genes might be promising targets in the treatment of AAA/RAAA.

Synchronous Type 3 EVAR Endoleaks at Multiple Sites Following Transfemoral Transcatheter Aortic Valve Replacement.

We describe a complication following transfemoral transcatheter aortic valve replacement in a patient who underwent remote endovascular abdominal aortic aneurysm repair. This report highlights technical complications to be vigilant of when using intravascular catheterization in patients with previous aneurysm repair while also showcasing synchronous type 3 endoleaks at multiple sites. (Level of Difficulty: Advanced.).

The Heart Team for Coronary Revascularization Decisions: 2 Illustrative Cases.

The 2021 ACC/AHA/SCAI coronary artery disease revascularization guideline highlights the importance of the multidisciplinary heart team in making patient-centered, evidence-based clinical decisions for patients considered for coronary revascularization. We present 2 cases highlighting aspects of heart team decision making for complex patients with coronary artery disease. (Level of Difficulty: Intermediate.).

Propionate Alleviates Abdominal Aortic Aneurysm by Modulating Colonic Regulatory T-Cell Expansion and Recirculation.

Emerging evidence supports that intestinal microbial metabolite short-chain fatty acids (SCFAs) increase the pool of regulatory T cells (Tregs) in the colonic lamina propria (cLP) and protect against nonintestinal inflammatory diseases, such as atherosclerosis and post-infarction myocardial inflammation. However, whether and how SCFAs protect the inflamed aortas of subjects with abdominal aortic aneurysm (AAA) remains unclear. Here, the authors revealed the protective effect of SCFAs on AAA in mice and the expansion of Tregs in the cLP, and propionate exerted Treg-dependent protection against AAA by promoting the recirculation of cLP-Tregs through colonic draining lymph nodes (dLNs) to the inflamed aorta.

N1-methyladenosine modification in cancer biology: Current status and future perspectives.

Post-transcriptional modifications in RNAs regulate their biological behaviors and functions. N1-methyladenosine (m1A), which is dynamically regulated by writers, erasers and readers, has been found as a reversible modification in tRNA, mRNA, rRNA and long non-coding RNA (lncRNA). m1A modification has impacts on the RNA processing, structure and functions of targets. Increasing studies reveal the critical roles of m1A modification and its regulators in tumorigenesis. Due to the positive relevance between m1A and cancer development, targeting m1A modification and m1A-related regulators has been of attention. In this review, we summarized the current understanding of m1A in RNAs, covering the modulation of m1A modification in cancer biology, as well as the possibility of targeting m1A modification as a potential target for cancer diagnosis and therapy.

The rupture of an abdominal aortic aneurysm at the level of horseshoe kidney: A case report.

Kidney anomalies are always a challenge even for the most experienced vascular and urologic surgeons in the reconstruction of the abdominal aortic segment. In the literature, the most common anomalies of the kidney are the horseshoe kidney. THE CASE: A 77-year-old male headed to the emergency department with complaints of acute abdominal pain and sudden onset of fatigue. The enhanced CT-scan performed and the horseshoe kidney with the ruptured aortic aneurysm seen. The cardiovascular and transplantation surgery team decided to perform explorative surgery.

Accessing 3D Printed Vascular Phantoms for Procedural Simulation.

Introduction: 3D printed patient-specific vascular phantoms provide superior anatomical insights for simulating complex endovascular procedures. Currently, lack of exposure to the technology poses a barrier for adoption. We offer an accessible, low-cost guide to producing vascular anatomical models using routine CT angiography, open source software packages and a variety of 3D printing technologies. Methods: Although applicable to all vascular territories, we illustrate our methodology using Abdominal Aortic Aneurysms (AAAs) due to the strong interest in this area. CT aortograms acquired as part of routine care were converted to representative patient-specific 3D models, and then printed using a variety of 3D printing technologies to assess their material suitability as aortic phantoms. Depending on the technology, phantoms cost $20-$1,000 and were produced in 12-48 h. This technique was used to generate hollow 3D printed thoracoabdominal aortas visible under fluoroscopy. Results: 3D printed AAA phantoms were a valuable addition to standard CT angiogram reconstructions in the simulation of complex cases, such as short or very angulated necks, or for positioning fenestrations in juxtarenal aneurysms. Hollow flexible models were particularly useful for device selection and in planning of fenestrated EVAR. In addition, these models have demonstrated utility other settings, such as patient education and engagement, and trainee and anatomical education. Further study is required to establish a material with optimal cost, haptic and fluoroscopic fidelity. Conclusion: We share our experiences and methodology for developing inexpensive 3D printed vascular phantoms which despite material limitations, successfully mimic the procedural challenges encountered during live endovascular surgery. As the technology continues to improve, 3D printed vascular phantoms have the potential to disrupt how endovascular procedures are planned and taught.

Collaborative Cardiac Care: A Comprehensive Heart Team Approach to Multiple Severe Vascular Conditions.

Left main artery coronary disease represents the highest risk lesion of ischemic heart disease. Revascularization can be accomplished by surgery or percutaneous interventions. This study highlights the case of a patient with severe multiple peripheral vascular conditions and complex coronary anatomy treated with percutaneous coronary intervention using mechanical circulatory support. (Level of Difficulty: Intermediate.).

Resolution of Inflammation Through the Lipoxin and ALX/FPR2 Receptor Pathway Protects Against Abdominal Aortic Aneurysms.

An abdominal aortic aneurysm (AAA) is a progressive aortic dilation that may lead to rupture, which is usually lethal. This study identifies the state of failure in the resolution of inflammation by means of decreased expression of the pro-resolving receptor A lipoxin/formyl peptide receptor 2 (ALX/FPR2) in the adventitia of human AAA lesions. Mimicking this condition by genetic deletion of the murine ALX/FPR2 ortholog in hyperlipidemic mice exacerbated the aortic dilation induced by angiotensin II infusion, associated with decreased vascular collagen and increased inflammation. The authors also identified key roles of lipoxin formation through 12/15-lipoxygenase and neutrophil p38 mitogen-activated protein kinase. In conclusion, this study established pro-resolving signaling by means of the ALX/FPR2 receptor in aneurysms and vascular inflammation.

Antagonism of toll-like receptor 2 attenuates the formation and progression of abdominal aortic aneurysm.

Abdominal aortic aneurysm (AAA) is an inflammatory vascular disorder with high mortality. Accumulating evidence shows that toll-like receptor 2 (TLR2) plays a critical role in the regulation of wound-repairing process after tissue injury. We wondered if TLR2 signaling contributed to the pathogenesis of AAA and that targeting TLR2 would attenuate AAA development and progression. In this study, enhanced expression of TLR2 and its ligands were observed in human AAA tissue. Neutralization of TLR2 protected against AAA development and caused established AAA to regress in mouse models of AAA. In addition, TLR2-deficient mice also failed to develop AAA. The prophylactic and therapeutic effects of blocking TLR2 were accompanied by a significant resolution of inflammation and vascular remodeling, as indicated by the decreased expression or activity of MMP-2/9, α-SMA, inflammatory cytokines, and transcription factors NF-κB, AP-1 and STAT1/3 in AAA tissue. Mechanistically, blocking TLR2 decreased the expression and interaction of TLR2 and several endogenous ligands, which diminished chronic inflammation and vascular remodeling in the vascular tissue of AAA. Our studies indicate that the interactions between TLR2 and its endogenous ligands contribute to the pathogenesis of AAA and that targeting TLR2 offers great potential toward the development of therapeutic agents against AAA.

Surgical treatment for saccular abdominal aortic aneurysms involving the renal artery origin: report of two cases.

We successfully treated small saccular abdominal aortic aneurysms involving the renal artery origin with direct sagittal suture closure under supra-celiac or supra-superior mesenteric artery cross clamping after renal artery reconstruction in two cases. This technique might be a useful option for localized saccular aortic aneurysms in selected cases.

Antagonism of toll-like receptor 2 attenuates the formation and progression of abdominal aortic aneurysm

Abdominal aortic aneurysm (AAA) is an inflammatory vascular disorder with high mortality. Accumulating evidence shows that toll-like receptor 2 (TLR2) plays a critical role in the regulation of wound-repairing process after tissue injury. We wondered if TLR2 signaling contributed to the pathogenesis of AAA and that targeting TLR2 would attenuate AAA development and progression. In this study, enhanced expression of TLR2 and its ligands were observed in human AAA tissue. Neutralization of TLR2 protected against AAA development and caused established AAA to regress in mouse models of AAA. In addition, TLR2-deficient mice also failed to develop AAA. The prophylactic and therapeutic effects of blocking TLR2 were accompanied by a significant resolution of inflammation and vascular remodeling, as indicated by the decreased expression or activity of MMP-2/9, α-SMA, inflammatory cytokines, and transcription factors NF-κB, AP-1 and STAT1/3 in AAA tissue. Mechanistically, blocking TLR2 decreased the expression and interaction of TLR2 and several endogenous ligands, which diminished chronic inflammation and vascular remodeling in the vascular tissue of AAA. Our studies indicate that the interactions between TLR2 and its endogenous ligands contribute to the pathogenesis of AAA and that targeting TLR2 offers great potential toward the development of therapeutic agents against AAA.