Histopathological evaluation of abdominal aortic aneurysms with deep learning.

Computational analysis of histopathological specimens holds promise in identifying biomarkers, elucidating disease mechanisms, and streamlining clinical diagnosis. However, the application of deep learning techniques in vascular pathology remains underexplored. Here, we present a comprehensive evaluation of deep learning-based approaches to analyze digital whole-slide images of abdominal aortic aneurysm samples from 369 patients from three European centers. Deep learning demonstrated robust performance in predicting inflammatory characteristics, particularly in the adventitia, as well as fibrosis grade and remaining elastic fibers in the tunica media. Overall, this study represents the first comprehensive evaluation of computational pathology in vascular disease and has the potential to contribute to improved understanding of abdominal aortic aneurysm pathophysiology and personalization of treatment strategies, particularly when integrated with radiological phenotypes and clinical outcomes.

Bypass Patency and Amputation-Free Survival after Popliteal Aneurysm Exclusion Significantly Depends on Patient Age and Medical Complications: A Detailed Dual-Center Analysis of 395 Consecutive Elective and Emergency Procedures.

Background/Objectives: A popliteal artery aneurysm (PAA) is traditionally treated by an open PAA repair (OPAR) with a popliteo-popliteal venous graft interposition. Although excellent outcomes have been reported in elective cases, the results are much worse in cases of emergency presentation or with the necessity of adjunct procedures. This study aimed to identify the risk factors that might decrease amputation-free survival (efficacy endpoint) and lower graft patency (technical endpoint). Patients and Methods: A dual-center retrospective analysis was performed from 2000 to 2021 covering all consecutive PAA repairs stratified for elective vs. emergency repair, considering the patient (i.e., age and comorbidities), PAA (i.e., diameter and tibial runoff vessels), and procedural characteristics (i.e., procedure time, material, and bypass configuration). Descriptive, univariate, and multivariate statistics were used. Results: In 316 patients (69.8 ± 10.5 years), 395 PAAs (mean diameter 31.9 ± 12.9 mm) were operated, 67 as an emergency procedure (6× rupture; 93.8% severe acute limb ischemia). The majority had OPAR (366 procedures). Emergency patients had worse pre- and postoperative tibial runoff, longer procedure times, and more complex reconstructions harboring a variety of adjunct procedures as well as more medical and surgical complications (all p < 0.001). Overall, the in-hospital major amputation rate and mortality rate were 3.6% and 0.8%, respectively. The median follow-up was 49 months. Five-year primary and secondary patency rates were 80% and 94.7%. Patency for venous grafts outperformed alloplastic and composite reconstructions (p < 0.001), but prolonged the average procedure time by 51.4 (24.3-78.6) min (p < 0.001). Amputation-free survival was significantly better after elective procedures (p < 0.001), but only during the early (in-hospital) phase. An increase in patient age and any medical complications were significant negative predictors, regardless of the aneurysm size. Conclusions: A popliteo-popliteal vein interposition remains the gold standard for treatment despite a probably longer procedure time for both elective and emergency PAA repairs. To determine the most effective treatment strategies for older and probably frailer patients, factors such as the aneurysm size and the patient's overall condition should be considered.

Mesenteric Ischemia after Cardiac Surgery.

BACKGROUND: Mesenteric ischemia (Me-Is) after cardiac surgery is underreported in present literature but has still earned the bad reputation of a dismal prognosis. This study adds clinical outcomes in a large patient cohort. METHODS: Between 2009 and 2019 of the 22,590 patients undergoing cardiac surgery at our facility 106 (0.47%) developed Me-Is postoperatively. Retrospective patient data was analyzed. Additionally, patients were stratified by outcome-survivors and nonsurvivors. RESULTS: Patients were predominantly male (n = 68, 64.2%), mean age was 71.2 ± 9.3 years. Most procedures were elective (n = 85, 80.2%) and comprised of more complex combined procedures (50.9%) and redos (17.9%). Mean EuroSCORE II averaged 10.9 ± 12.2%. Survival at 30 days was 49.1% (n = 52). Clinical baseline and procedural characteristics did not differ significantly between survivors and nonsurvivors. The median postoperative interval until symptom onset was 5 days in both groups. Survivors were more frequently diagnosed by computed tomography and nonsurvivors based on clinical symptoms. Me-Is was predominantly nonocclusive (n = 84, 79.2%). Laparotomy was the main treatment in both groups (n = 45, 78.8% vs. n = 48, 88.9%, p = 0.94). Predictors of mortality were maximum norepinephrine doses (hazard ratio [HR] 8.29, confidence interval [CI] 3.39-20.26, p < 0.0001), lactate levels (HR 1.06, CI 1.03-1.09), and usage of inotropes (HR 2.46, CI 1.41-4.30). CONCLUSION: The prognosis of Me-Is following cardiac surgery is poor-independently from diagnostic or treatment patterns. There exists a significant asymptomatic time period postoperatively, in which pathophysiologic processes seem to cross the Rubicon. After clinical demarcation, the further course can almost no longer be influenced.

Reducing Abdominal Aortic Aneurysm Progression by Blocking Neutrophil Extracellular Traps Depends on Thrombus Formation.

Neutrophil extracellular traps (NETs) are implicated in the pathogenesis of abdominal aortic aneurysm (AAA), located in adventitia and intraluminal thrombus. We compared the therapeutic potential of targeting upstream or downstream effector molecules of NET formation in 2 murine AAA models based on angiotensin II or peri-adventitial elastase application. In both models, NETs were detected in formed aneurysms at treatment start. Although NET inhibitors failed in the elastase model, they prevented progression of angiotensin II-induced aneurysms with thrombus, which resembles established human disease (including thrombus development). Blockade of upstream NET mediators was more effective than interference with downstream NET molecules.

[Ischemia-related compartment syndromes in vascular surgery]. / Ischämisch bedingte Kompartmentsyndrome in der Gefäßchirurgie.

Even after the endovascular revolution, acute compartment syndrome (CS) remains an important and frequently present differential diagnosis after many operations. Based on a qualitative review this article gives an overview of the most frequent forms of CS as well as some less frequent entities that require attention in the routine clinical practice. Additionally, the pathophysiology, diagnostics and treatment as well as current research topics for CS, especially concerning the lower leg, are dealt with in detail. In summary, nothing has essentially changed ever since the first description of CS in that the clinical estimation remains the gold standard. The detection and the adequate treatment especially of abdominal CS and CS of the lower leg remain a key competence of vascular surgeons.

Outcome of Endovascular and Open Treated Penetrating Aortic Ulcers.

PURPOSE: Penetrating aortic ulcer (PAU) is a rare etiology of acute aortic syndrome. Few studies exist regarding the perioperative outcome. The aim was to analyze clinical outcome and risk factors of mortality in this treatment population. METHODS: Retrospective, monocentric study from 2010 to 2021. Clinical data of endovascular or open treated PAU were analyzed. In-hospital mortality was selected as the primary study endpoint. Angio-morphologies were analyzed and risk factors for mortality were identified by using univariate analysis. RESULTS: Overall, 133 patients were identified. 29% (n=38) of patients presented symptomatically. In 64% (n=85), the PAU was localized in the thoracic aorta. On average, PAUs had a depth of 15.4±10.1 mm and a width of 17.9±9.6 mm. The patients had a median of 2 (95% confidence interval [CI]=2-3) high-risk features (HRF) as PAU depth >10 mm, PAU width >20 mm, aortic diameter >40 mm, symptomatic, intramural hematoma (IMH), pleural effusion. Significantly more HRF were observed in symptomatic patients (p=0.01). 53% (n=71) of patients were treated with thoracic endovascular aortic repair (TEVAR), 41% (n=54) by endovascular aortic repair (EVAR), and 6% (n=8) by open surgery. A hybrid procedure with cervical debranching was performed in 16% (n=21) and complex endovascular repair with fenestrated or branched endografts in 15% (n=20). Overall, complications greater than grade II according to the Clavien-Dindo classification occurred in 19% (n=25) and of the patients. In-hospital mortality manifested in 6% (n=8). Factors associated with increased mortality were the diameter of the aorta >40 mm (88% vs 39%, p=0.03), as well as symptomatic patients (63% vs 26%, p=0.04), coincident IMHs (38% vs 10%, p=0.05), and complex endovascular procedures (50% vs 50% p<0.01). Penetrating aortic ulcer width >20 mm tended to show higher mortality (75% vs 40%, p=0.06). Routine follow-up was available for 89% (n=117) for a median of 39 months (95% CI=25-42). One-year and 5-year survival were 83% and 60%, respectively, with 1 aortic pathology-related death. CONCLUSIONS: Treatment of PAU is associated with an acceptable perioperative morbidity and mortality. Risk factors associated with increased mortality are an elevated aortic diameter, the presence of IMHs, clinical symptomatology at presentation, and complex endovascular procedures.

Open Retrograde Stenting of Proximal Innominate and Common Carotid Artery Stenosis.

PURPOSE: The evidence regarding the treatment of open retrograde stenting of innominate artery (IA) or common carotid artery stenosis (CCA) is limited, and is suspected to carry a high risk of stroke and death. Therefore, the objective of this study was to evaluate the outcomes of such hybrid procedures. METHODS: A retrospective, monocentric study of all patients who underwent retrograde stenting of proximal IA and CCA stenosis via surgical cutdown of the CCA, with or without concomitant CEA, between 2016 and 2023 was performed. RESULTS: Overall, 33 patients were treated. A total of 15 patients (45.5%) were male, with the mean age being 67 ± 9.1 years, and 58% (n = 19) of the patients presented with neurological symptoms. Open retrograde stenting was performed in 67% (n = 22) in ACC, and in 33% (n = 11) in IA stenosis. A total of 20 patients (61%) underwent retrograde stenting with synchronous ipsilateral CEA for concomitant stenosis of the carotid bifurcation. There was no 30-day mortality. The perioperative stroke rate was 3% (n = 1) with complete symptom recovery. During the follow up at 32 months (95% CI: 24-39), three late deaths (9.1%) and one symptomatic stent occlusion were observed and, in five patients (15.2%), re-intervention for restenosis was necessary. CONCLUSIONS: Open retrograde stenting for of proximal IA or CCA stenosis with or without CEA, in case of tandem carotid lesions, can be performed safely with a low rate of early adverse events. Continuous follow up examinations are necessary due to relevant instent re-stenosis rates.

Physician-made pericardium stent graft as a potential endovascular alternative for infectious aortic disease - an ex-vivo proof-of-concept study.

PURPOSE.: The treatment of infectious aortic disease is still challenging with open surgical debridement and reconstruction using biological, preferably autologous material, being the treatment of choice. However, these procedures are associated with high morbidity and mortality. Endovascular therapy is often considered a bridging method only, since the biologically inactive fabric of the covered stent grafts usually cannot be treated sufficiently with anti-infective agents in the event of a (obligate) consecutive secondary graft infection. This study aims to prove the feasibility of a physician-made pericardium stent graft ex-vivo. TECHNIQUE.: A state-of-the-art TEVAR was modified by separating the fabric from the z-stents and suturing a hand-sewn bovine pericardium tube to the bare metal. Feasibility of preparation, re-sheathing, and delivery is demonstrated in an ex-vivo model. CONCLUSION.: This first xenogeneic stent graft could be manufactured and deployed successfully. In the future this may provide a bridging alternative for high-risk patients with infected native aortic aneurysm or aortic fistulas, eventually followed by surgical or thoracoscopic/laparoscopic debridement. Further studies on simulators or animal models are needed to test the technique and investigate its long-term durability. Additionally, this study prompts reflection on whether materials currently used should be further developed to prevent graft infections.

Aortic Vascular Graft and Endograft Infection-Patient Outcome Cannot Be Determined Based on Pre-Operative Characteristics.

Vascular graft/endograft infection (VGEI) is a serious complication after aortic surgery. This study investigates VGEI and patient characteristics, PET/CT quantification before surgical or conservative management of VGEI and post-intervention outcomes in order to identify patients who might benefit from such a procedure. PET standard uptake values (SUV) were quantitatively assessed and compared to a non-VGEI cohort. The primary endpoints were in-hospital mortality and aortic reintervention-free survival at six months. Ninety-three patients (75% male, 65 ± 10 years, 82% operated) were included. The initial operation was mainly for aneurysm (67.7%: 31% EVAR, 12% TEVAR, 57% open aortic repair). Thirty-two patients presented with fistulae. PET SUVTLR (target-to-liver ratio) showed 94% sensitivity and 89% specificity. Replacement included silver-coated Dacron (21.3%), pericardium (61.3%) and femoral vein (17.3%), yet the material did not influence the overall survival (p = 0.745). In-hospital mortality did not differ between operative and conservative treatment (19.7% vs. 17.6%, p = 0.84). At six months, 50% of the operated cohort survived without aortic reintervention. Short- and midterm morbidity and mortality remained high after aortic graft removal. Neither preoperative characteristics nor the material used for reconstruction influenced the overall survival, and, with limitations, both the in-hospital and midterm survival were similar between the surgically and conservatively managed patients.

A Modern Series of Secondary Aortoenteric Fistula - A 19-Year Experience.

OBJECTIVES: Secondary aortoenteric fistula is a rare and life-threatening condition. Clear evidence on the ideal therapeutic approach is largely missing. This study aims to analyze symptoms, etiology, risk factors, and outcomes based on procedural details. PATIENTS AND METHODS: All patients with secondary aortoenteric fistula admitted between 2003 and 2021 were included. Patient characteristics, surgical procedure details, and postoperative outcomes were analyzed. Outcomes were stratified and compared according to the urgency of operation and the procedure performed. Descriptive statistics were used. The primary endpoint was in-hospital mortality. RESULTS: A total of twentytwo patients (68% male, median age 70 years) were identified. Main symptoms were gastrointestinal bleeding, pain, and fever. From the twentytwo patients ten patients required emergency surgery and ten urgent surgery. Emergency patients were older on average (74 vs 63 years, P = .015) and had a higher risk of postoperative respiratory complications (80% vs 10%, P = .005). Primary open surgery with direct replacement of the aorta or an extra-anatomic bypass with an additional direct suture or resection of the involved bowel was performed in sixteen patients. In four patients underwent endovascular bridging treatment with the definitive approach as a second step. Other two patients died without operation (1x refusal; 1x palliative cancer history). In-hospital mortality was 27%, respectively. Compared to patients undergoing urgent surgery, those treated emergently showed significantly higher in-hospital (50% vs 0%, P = .0033) mortalities. CONCLUSION: Despite rapid diagnosis and treatment, secondary aortoenteric fistula remains a life-threatening condition with 27% in-hospital mortality, significantly increased upon emergency presentation.

Utilization of an Artery-on-a-Chip to Unravel Novel Regulators and Therapeutic Targets in Vascular Diseases.

In this study, organ-on-chip technology is used to develop an in vitro model of medium-to-large size arteries, the artery-on-a-chip (AoC), with the objective to recapitulate the structure of the arterial wall and the relevant hemodynamic forces affecting luminal cells. AoCs exposed either to in vivo-like shear stress values or kept in static conditions are assessed to generate a panel of novel genes modulated by shear stress. Considering the crucial role played by shear stress alterations in carotid arteries affected by atherosclerosis (CAD) and abdominal aortic aneurysms (AAA) disease development/progression, a patient cohort of hemodynamically relevant specimens is utilized, consisting of diseased and non-diseased (internal control) vessel regions from the same patient. Genes activated by shear stress follow the same expression pattern in non-diseased segments of human vessels. Single cell RNA sequencing (scRNA-seq) enables to discriminate the unique cell subpopulations between non-diseased and diseased vessel portions, revealing an enrichment of flow activated genes in structural cells originating from non-diseased specimens. Furthermore, the AoC served as a platform for drug-testing. It reproduced the effects of a therapeutic agent (lenvatinib) previously used in preclinical AAA studies, therefore extending the understanding of its therapeutic effect through a multicellular structure.

Outcome After Conservative and Endovascular Treatment of Stanford Type B Aortic Intramural Hematomas - A Single-Center Retrospective Study.

OBJECTIVES: Aortic intramural hematoma (IMH) is a rare disease. Thus far, only limited data is available and the indications for conservative and endovascular treatment are not well defined. The aim of this study was to investigate clinical presentation, course, CT imaging features and outcome of patients with type B aortic IMHs. METHODS: We included all patients with type B IMHs between 2012 and 2021 in this retrospective monocentric study. Clinical data, localization, thickness of IMHs and the presence of ulcer-like projections (ULPs) was evaluated before and after treatment. RESULTS: Thirty five patients (20 females; 70.3 y ± 11 y) were identified. Almost all IMHs (n = 34) were spontaneous and symptomatic with back pain (n = 34). At the time of diagnosis, TEVAR was deemed indicated in 9 patients, 26 patients were treated primarily conservatively. During the follow-up, in another 16 patients TEVAR was deemed indicated. Endovascularly and conservatively treated patients both showed decrease in thickness after treatment. Patients without ULPs showed more often complete resolution of the IMH than patients with ULPs (endovascularly treated 90.9% (10/11) vs 71.4% (5/7); conservatively treated 71.4% (10/14) vs 33.3% (1/3); P = .207). Complications after TEVAR occurred in 32% and more frequently in patients treated primarily conservatively (37.5% vs 22.2%). No in-hospital mortality was observed during follow-up. CONCLUSIONS: Prognosis of IMH seems favourable in both surgically as well as conservatively treated patients. However, it is essential to identify patients at high risk for complications under conservative treatment, who therefore should be treated by TEVAR. In our study, ULPs seem to be an adverse factor for remodeling.

Radiation therapy for cancer is potentially associated with reduced growth of concomitant abdominal aortic aneurysm.

PURPOSE: Co-prevalence of abdominal aortic aneurysm (AAA) and cancer poses a unique challenge in medical care since both diseases and their respective therapies might interact. Recently, reduced AAA growth rates were observed in cancer patients that received radiation therapy (RT). The purpose of this study was to perform a fine-grained analysis of the effects of RT on AAA growth with respect to direct (infield) and out-of-field (outfield) radiation exposure, and radiation dose-dependency. METHODS: A retrospective single-center analysis identified patients with AAA, cancer, and RT. Clinical data, radiation plans, and aneurysm diameters were analyzed. The total dose of radiation to each aneurysm was computed. AAA growth under infield and outfield exposure was compared to patients with AAA and cancer that did not receive RT (no-RT control) and to an external noncancer AAA reference cohort. RESULTS: Between 2003 and 2020, a total of 38 AAA patients who had received well-documented RT for their malignancy were identified. AAA growth was considerably reduced for infield patients (n = 18) compared to outfield patients (n = 20), albeit not significantly (0.8 ± 1.0 vs. 1.3 ± 1.6 mm/year, p = 0.28). Overall, annual AAA growth in RT patients was lower compared to no-RT control patients (1.1 ± 1.5 vs. 1.8 ± 2.2 mm/year, p = 0.06) and significantly reduced compared to the reference cohort (1.1 ± 1.5 vs. 2.7 ± 2.1 mm/year, p < 0.001). The pattern of AAA growth reduction due to RT was corroborated in linear regression analyses correcting for initial AAA diameter. A further investigation with respect to dose-dependency of radiation effects on AAA growth, however, revealed no apparent association. CONCLUSION: In this study, both infield and outfield radiation exposure were associated with reduced AAA growth. This finding warrants further investigation, both in a larger scale clinical cohort and on a molecular level.

Patients with Acute Limb Ischemia Might Benefit from Endovascular Therapy-A 17-Year Retrospective Single-Center Series of 985 Patients.

Acute lower limb ischemia (ALI) is a common vascular emergency, requiring urgent revascularization by open or endovascular means. The aim of this retrospective study was to evaluate patient demographics, treatment and periprocedural variables affecting the outcome in ALI patients in a consecutive cohort in a tertiary referral center. Primary outcome events (POE) were 30-day (safety) and 180-day (efficacy) combined mortality and major amputation rates, respectively. Secondary outcomes were perioperative medical and surgical leg-related complications and the 5-year combined mortality and major amputation rate. Statistical analysis used descriptive and uni- and multivariable Cox regression analysis. In 985 patients (71 ± 9 years, 56% men) from 2004 to 2020, the 30-day and 180-day combined mortality and major amputation rates were 15% and 27%. Upon multivariable analysis, older age (30 d: aHR 1.17; 180 d: 1.27) and advanced Rutherford ischemia stage significantly worsened the safety and efficacy POE (30 d: TASC IIa aHR 3.29, TASC IIb aHR 3.93, TASC III aHR 7.79; 180 d: TASC IIa aHR 1.97, TASC IIb aHR 2.43, TASC III aHR 4.2), while endovascular treatment was associated with significant improved POE after 30 days (aHR 0.35) and 180 days (aHR 0.39), respectively. Looking at five consecutive patient quintiles, a significant increase in endovascular procedures especially in the last quintile could be observed (17.5% to 39.5%, p < 0.001). Simultaneously, the re-occlusion rate as well as the number of patients with any previous revascularization increased. In conclusion, despite a slightly increasing early re-occlusion rate, endovascular treatment might, if possible, be favorable in ALI treatment.

The circular RNA Ataxia Telangiectasia Mutated regulates oxidative stress in smooth muscle cells in expanding abdominal aortic aneurysms.

An abdominal aortic aneurysm (AAA) is a pathological widening of the aortic wall characterized by loss of smooth muscle cells (SMCs), extracellular matrix degradation, and local inflammation. This condition is often asymptomatic until rupture occurs, leading to high morbidity and mortality rates. Diagnosis is mostly accidental and the only currently available treatment option remains surgical intervention. Circular RNAs (circRNAs) represent a novel class of regulatory non-coding RNAs that originate from backsplicing. Their highly stable loop structure, combined with a remarkable enrichment in body fluids, make circRNAs promising disease biomarkers. We investigated the contribution of circRNAs to AAA pathogenesis and their potential application to improve AAA diagnostics. Gene expression analysis revealed the presence of deregulated circular transcripts stemming from AAA-relevant gene loci. Among these, the circRNA to the Ataxia Telangiectasia Mutated gene (cATM) was upregulated in human AAA specimens, in AAA-derived SMCs, and serum samples collected from aneurysm patients. In primary aortic SMCs, cATM increased upon angiotensin II and doxorubicin stimulation, while its silencing triggered apoptosis. Higher cATM levels made AAA-derived SMCs less vulnerable to oxidative stress, compared with control SMCs. These data suggest that cATM contributes to elicit an adaptive oxidative-stress response in SMCs and provides a reliable AAA disease signature.

Single-center initial experience with inner-branch complex EVAR in 44 patients.

Purpose: The use of inner-branch aortic stent grafts in the treatment of complex aortic pathologies aims at broad applicability and stable bridging stent sealing compared to other endovascular technologies. The objective of this study was to evaluate the early outcomes with a single manufacturer custom-made and off-the-shelf inner-branched endograft in a mixed patient cohort. Methods: This retrospective, monocentric study between 2019 and 2022 included 44 patients treated with inner-branched aortic stent grafts (iBEVAR) as custom-made device (CMD) or off-the-shelf device (E-nside) with at least four inner branches. The primary endpoints were technical and clinical success. Results: Overall, 77% (n = 34) and 23% (n = 10) of the patients (mean age 77 ± 6.5 years, n = 36 male) were treated with a custom-made iBEVAR with at least four inner branches and an off-the-shelf graft, respectively. Treatment indications were thoracoabdominal pathologies in 52.2% (n = 23), complex abdominal aneurysms in 25% (n = 11), and type Ia endoleaks in 22.7% (n = 10). Preoperative spinal catheter placement was performed in 27% (n = 12) of patients. Implantation was entirely percutaneous in 75% (n = 33). Technical success was 100%. Target vessel success manifested at 99% (178/180). There was no in-hospital mortality. Permanent paraplegia developed in 6.8% (n = 3) of patients. The mean follow-up was 12 months (range 0-52 months). Three late deaths (6.8%) occurred, one related to an aortic graft infection. Kaplan-Meier estimated 1-year survival manifested at 95% and branch patency at 98% (177/180). Re-intervention was necessary for a total of six patients (13.6%). Conclusions: Inner-branch aortic stent grafts provide a feasible option for the treatment of complex aortic pathologies, both elective (custom-made) and urgent (off-the-shelf). The technical success rate is high with acceptable short-term outcomes and moderate re-intervention rates comparable to existing platforms. Further follow-up will evaluate long-term outcomes.

Apolipoprotein E (ApoE) Rescues the Contractile Smooth Muscle Cell Phenotype in Popliteal Artery Aneurysm Disease.

Popliteal artery aneurysm (PAA) is the most frequent peripheral aneurysm, primarily seen in male smokers with a prevalence below 1%. This exploratory study aims to shed light on cellular mechanisms involved in PAA progression. Sixteen human PAA and eight non-aneurysmatic popliteal artery samples, partially from the same patients, were analyzed by immunohistochemistry, fluorescence imaging, Affymetrix mRNA expression profiling, qPCR and OLink proteomics, and compared to atherosclerotic (n = 6) and abdominal aortic aneurysm (AAA) tissue (n = 19). Additionally, primary cell culture of PAA-derived vascular smooth muscle cells (VSMC) was established for modulation and growth analysis. Compared to non-aneurysmatic popliteal arteries, VSMCs lose the contractile phenotype and the cell proliferation rate increases significantly in PAA. Array analysis identified APOE higher expressed in PAA samples, co-localizing with VSMCs. APOE stimulation of primary human PAA VSMCs significantly reduced cell proliferation. Accordingly, contractile VSMC markers were significantly upregulated. A single case of osseous mechanically induced PAA with a non-diseased VSMC profile emphasizes these findings. Carefully concluded, PAA pathogenesis shows similar features to AAA, yet the mechanisms involved might differ. APOE is specifically higher expressed in PAA tissue and could be involved in VSMC phenotype rescue.

Associations of Tissue and Soluble LOX-1 with Human Abdominal Aortic Aneurysm.

Background Indication for prophylactic surgical abdominal aortic aneurysm (AAA) repair depends on the maximal aortic diameter. The lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is the major receptor for uptake of oxidized low-density lipoprotein cholesterol and is implicated in atherosclerosis. A soluble form of LOX-1 (sLOX-1) has been discussed as a novel biomarker in coronary artery disease and stroke. Herein, we assessed the regulation of aortic LOX-1 as well as the diagnostic and risk stratification potential of sLOX-1 in patients with AAA. Methods and Results Serum sLOX-1 was assessed in a case-control study in AAA (n=104) and peripheral artery disease (n=104). sLOX-1 was not statistically different between AAA and peripheral artery disease but was higher in AAA (ß=1.28, P=0.04) after adjusting for age, atherosclerosis, type 2 diabetes, prescription of statins, ß-blockers, ACE inhibitors, and therapeutic anticoagulation. sLOX-1 was not associated with the aortic diameter, AAA volume, or the thickness of the intraluminal thrombus. Aortic LOX-1 mRNA expression tended to be higher in AAA when compared with disease, and expression was positively associated with cleaved caspase-3, smooth muscle actin, collagen, and macrophage content. Conclusions In AAA, sLOX-1 was differently affected by age, cardiometabolic diseases, and corresponding medical therapies. Comparison with nonatherosclerotic disease would be beneficial to further elucidate the diagnostic potential of sLOX-1, although it was not useful for risk stratification. Aneurysmal LOX-1 mRNA expression was increased and positively associated with smooth muscle cells and collagen content, suggesting that LOX-1 is eventually not deleterious in human AAA and could counteract AAA rupture.