Hypoxia Marker Carbonic Anhydrase IX Is Present in Abdominal Aortic Aneurysm Tissue and Plasma

Abdominal aortic aneurysms (AAA) are a significant cause of premature deaths worldwide. Since there is no specific treatment for reducing AAA progression, it is crucial to understand the pathogenesis leading to aneurysm wall weakening/remodeling and identify new proteins involved in this process which could subsequently serve as novel therapeutic targets. In this study, we analyzed the presence of the hypoxia-related proteins carbonic anhydrase IX (CA IX), hypoxia-inducible factor 1α (HIF-1α), and AKT as the key molecule in the phosphoinositide-3-kinase pathway in the AAA wall. Additionally, we used a blood-based assay to examine soluble CA IX (s-CA IX) levels in the plasma of AAA patients. Using western blotting, we detected CA IX protein in 12 out of 15 AAA tissue samples. Immunohistochemistry staining proved CA IX expression in the media of the aneurysmal wall. Evaluation of phosphorylated (p-AKT) and total AKT showed elevated levels of both forms in AAA compared to normal aorta. Using ELISA, we determined the concentration of s-CA IX >20 pg/mL in 13 out of 15 AAA patients. Results obtained from in silico analysis of CA9 and aneurysm-associated genes suggest a role for CA IX in aneurysmal wall remodeling. Our results prove the presence of hypoxia-related CA IX in AAA tissues and indicate a possible role of CA IX in hypoxia-associated cardiovascular diseases.

Blood Biomarkers and Serologic Immunological Profiles Related to Periodontitis in Abdominal Aortic Aneurysm Patients

BackgroundPeriodontitis is a chronic inflammatory gum disease associated with systemic diseases such as cardiovascular diseases.AimTo investigate the association of systemic blood biomarkers, C-reactive protein (CRP), levels of lipopolysaccharide (LPS), and IgG levels against periodontal pathogens Aggregatibacter actinomycetemcomitans (Aa) and Porphyromonas gingivalis (Pg) with the stability, based on the aortic diameter, the growth rate and the eligibility for surgical intervention, of patients with abdominal aortic aneurysm (AAA).MethodsPatients with stable AAA (n = 30) and unstable AAA (n = 31) were recruited. The anti-A. actinomycetemcomitans and anti-P. gingivalis IgG levels were analyzed by ELISA, the LPS analysis was performed by using the limulus amebocyte lysate (LAL) test, and plasma levels of CRP were determined using an immune turbidimetric method. The association between these blood systemic biomarkers, AAA features, periodontal clinical parameters and oral microbial profiles were explored. Regression models were used to test the relationship between variables.ResultsThe presence of antibodies against Pg and Aa, LPS and high CRP concentrations were found in all AAA patients. The IgG levels were similar in patients with stable and unstable AAA (both for Aa and Pg). Among investigated blood biomarkers, only CRP was associated with AAA stability. The amount of LPS in saliva, supra, and subgingival plaque were significantly associated with the systemic LPS (p <0.05).ConclusionsThis post-hoc study emphasizes the presence of antibodies against Pg and Aa, LPS and high CRP concentrations in all AAA patients. The presence of Pg in saliva and subgingival plaque was significantly associated with the blood LPS levels. For further studies investigating periodontitis and systemic diseases, specific predictive blood biomarkers should be considered instead of the use of antibodies alone.

Change in Abdominal Aortic Aneurysm Sac Diameter After Endovascular Repair: A Single-Center Experience From Taiwan

Purpose: The purpose of this study was to investigate the change in the diameter of infrarenal abdominal aortic aneurysm (AAA) sacs after endovascular aortic repair (EVAR) in Taiwanese patients and to depict its association with clinical outcomes. Materials and Methods: This retrospective cohort study was conducted on patients who underwent EVAR for infrarenal AAA between January 2011 and December 2016. All preoperative and follow-up computed tomography (CT) images were reviewed. Postoperative CT angiography was arranged after 1 month and annually thereafter. The maximal diameter on the axial plane and the maximal diameter perpendicular to the centerline on the coronal and sagittal planes were measured. The study examined post-EVAR sac diameter change over time and compared the differences in adverse events (AEs) among groups. Results: The survey included a total of 191 patients with a median follow-up duration of 2.5 (interquartile range: 1.1–2.9) years. Overall survival rates at 1, 2, and 5 years were 92%, 81%, and 76%, respectively. According to their last CT scans, the patients were categorized into 3 groups as follows: shrinkage, stationary, and enlargement, which comprised 58 (30.4%), 118 (61.8%), and 15 (7.9%) patients, respectively. Pre-EVAR characteristics and sac diameters were similar among the groups. Sac shrinkage was exclusively observed in the first 2 years, whereas sac enlargement developed at all follow-up periods. Patients with sac enlargement had higher incidence rates of endoleaks, complications, and reintervention than the other groups. Conclusion: Based on our observations, post-EVAR sac shrinkage only occurs in the first 2 years; however, post-EVAR sacs may enlarge at any point and even after 5 years. In our study, patients with sac enlargement had higher rates of adverse events and reintervention.

Photocrosslinking of Adventitial Collagen in the Porcine Abdominal Aorta: A Preliminary Approach to a Strategy for Prevention of Aneurysmal Rupture

This study was aimed at generating data for designing a potential method to prevent the rupture of the abdominal aortic aneurysm (AAA). We found that the mechanical strength and stiffness of blood vessel walls was enhanced by the crosslinking of adventitial collagen through a photochemical process promoted by ultraviolet-A (UV-A) radiation. The experiments were carried out on samples isolated from 25 normal porcine aortas. The adventitial layer was separated from the other layers and exposed to UV radiation of 365-nm wavelength, in the presence of a riboflavin compound as the photosensitizer. Mechanical testing of 30 specimens, prior to and after exposure, indicated an increase in both strength (ultimate stress) and stiffness (Young’s modulus) of the adventitial specimens following irradiation. The crosslinking process also led to an enhanced resistance to experimental collagenolysis, as determined on six specimens. At this phase of conceptual design, we suggest that by applying this method to an aneurysmal dilated wall region, the stabilization of tunica adventitia may delay or prevent the rupture of the aneurysm and, with further investigation and refinement, can become a therapeutic strategy for arresting the progression of AAA.

Prospective Comparison of Plasma Biomarker and Traditional Risk Factor Profiles for Incident Isolated Atherosclerotic Disease and Incident Isolated Abdominal Aortic Aneurysm

Background: Traditional risk factors for atherosclerotic disease (AD) are well-known, of which some are relevant also for abdominal aortic aneurysms (AAA). The present study compares the importance of plasma biomarkers and traditional risk factor profiles for incident AD without concomitant AAA (isolated AD) and AAA without concomitant AD (isolated AAA) during long-term follow-up.Methods: In the Malmö Diet and Cancer Study—cardiovascular cohort, 5,381 participants were free from atrial fibrillation or flutter, AD (coronary artery disease, atherothrombotic ischemic stroke, carotid artery disease, or peripheral artery disease), and AAA underwent blood sampling under standardized fasting conditions between 1991 and 1994. Cox proportional hazards regression analysis was used to calculate hazard ratios (HR) with 95% CIs.Results: During a median follow-up of 23.1 years, 1,152 participants developed isolated AD, and 44 developed isolated AAA. Adjusted HR for lipoprotein-associated phospholipase A2 (mass) (HR 1.53, 95% CI 1.14–2.04 vs. HR 1.05, 95% CI.99–1.12) was higher for incident isolated AAA compared to incident isolated AD, respectively. Mid-regional pro-adrenomedullin (MR-proADM) was associated with incident isolated AD (HR 1.17, 95% CI 1.1–1.25) and incident isolated AAA (HR 1.47, 95% CI 1.15–1.88). MR-proADM was correlated (r = 0.32; p < 0.001) to body mass index (BMI), and BMI was associated with increased risk of incident isolated AAA (HR 1.43, 95% CI 1.02–2). No participant with diabetes mellitus (DM) at baseline developed isolated AAA (0/44), whereas DM was associated with an increased risk of isolated AD (HR 2.57, 95% CI 2.08–3.18). Adjusted HR for male sex (HR 4.8, 95% CI 2.42–9.48, vs. HR 1.76, 95% CI 1.56–1.98) and current smoking (HR 4.79, 95% CI 2.42–9.47 vs. HR 1.97, 95% CI 1.73–2.23) were higher in the incident isolated AAA group compared to the incident isolated AD group, respectively.Conclusions: The data supports the view that components of vascular inflammation and cardiovascular stress drives AAA development, whereas glycated cross-links in abdominal aortic wall tissue may have a plausible role in reducing AAA risk in individuals with DM.

Concomitant Radical Cystectomy and Infrarenal Aortic Aneurysm Repair with Cryopreserved Aortic Allograft: A Case Report

In localized muscle invasive bladder cancer (MIBC), the gold standard treatment is radical cystectomy (RC) with bilateral pelvic lymph node dissection (PLND), associated with cisplatin-based neoadjuvant chemotherapy, whereas first-line treatment for metastatic patients is cisplatin-based chemotherapy. In men with an abdominal aortic aneurysm (AAA), elective repair is recommended when its diameter is >5.5 cm, while cryopreserved arterial allografts (CAA) offer resistance to infection. A patient with simultaneous metastatic MIBC, associated with left hydronephrosis, and infrarenal AAA of 49 mm diameter was evaluated in an interdisciplinary study. Concomitant surgery was opted for; first, the AAA repair with CAA implantation was practiced, followed by retroperitoneal and common iliac lymphadenectomy. Thereafter, RC and PLND were conducted, and a Wallace-1 ileal conduit and a stoma were constructed. Chest and abdomen contrast-enhanced CT at 2 months showed the onset of two osteolytic lesions on the left ilium. At oncological re-evaluation the patient was deemed cisplatin-fit.