Histopathological Characterization of Abdominal Aortic Aneurysms from Patients with Multiple Aneurysms Compared to Patients with a Single Abdominal Aortic Aneurysm.

The aim of this study was to investigate histopathological differences in abdominal aortic aneurysms (AAAs) between patients with multiple and single arterial aneurysms, as we suspect that there are different underlying mechanisms in aneurysm formation. Analysis was based on a previous retrospective study on patients with multiple arterial aneurysms (mult-AA; defined as at least four, n = 143) and a single AAA (sing-AAA, n = 972) who were admitted to our hospital for treatment between 2006 and 2016. Available paraffin-embedded AAA wall specimens were derived from the Vascular Biomaterial Bank Heidelberg (mult-AA, n = 12 vs. sing-AAA, n = 19). Sections were analyzed regarding structural damage of the fibrous connective tissue and inflammatory cell infiltration. Alterations to the collagen and elastin constitution were assessed by Masson-Goldner trichrome and Elastica van Gieson staining. Inflammatory cell infiltration, response and transformation were assessed by CD45 and IL-1ß immunohistochemistry and von Kossa staining. The extent of aneurysmal wall alterations was assessed by semiquantitative gradings and was compared between the groups using Fisher's exact test. IL-1ß was significantly more present in the tunica media in mult-AA compared to sing-AAA (p = 0.022). The increased expression of IL-1ß in mult-AA compared to sing-AAA indicates inflammatory processes play a role in aneurysm formation in patients with multiple arterial aneurysms.

Mitochondrial Dysfunction and Increased DNA Damage in Vascular Smooth Muscle Cells of Abdominal Aortic Aneurysm (AAA-SMC).

There is increasing evidence for enhanced oxidative stress in the vascular wall of abdominal aortic aneurysms (AAA). Mitochondrial damage and dysfunction are hypothesized to be actors in altered production of reactive oxygen species (ROS) and oxidative stress. However, the role of mitochondria and oxidative stress in vascular remodelling and progression of AAA remains uncertain. We here addressed whether mitochondrial dysfunction is persistently increased in vascular smooth muscle cells (VSMCs) isolated from AAA compared to healthy VSMC. AAA-derived VSMC cultures (AAA-SMC, n = 10) and normal VSMC cultures derived from healthy donors (n = 7) were grown in vitro and analysed for four parameters, indicating mitochondrial dysfunction: (i) mitochondrial content and morphology, (ii) ROS production and antioxidative response, (iii) NADP+/NADPH content and ratio, and (iv) DNA damage, in the presence or absence of angiotensin II (AngII). AAA-SMC displayed increased mitochondrial circularity (rounded shape), reduced mitochondrial area, and reduced perimeter, indicating increased fragmentation and dysfunction compared to healthy controls. This was accompanied by significantly increased O2 - production, reduced NADP+/NADPH levels, a lower antioxidative response (indicated by antioxidative response element- (ARE-) driven luciferase reporter assays), more DNA damage (determined by percentage of γ-H2A.X-positive nuclei), and earlier growth arrest in AAA-SMC. Our data suggest that mitochondrial dysfunction and oxidative stress are persistently increased in AAA-SMC, emphasizing their implication in the pathophysiology of AAA.

Thoracic Endovascular Aortic Repair (TEVAR) First in Patients with Lower Limb Ischemia in Complicated Type B Aortic Dissection: Clinical Outcome and Morphology.

Acute Type B aortic dissection (TBAD) can cause organ malperfusion, e.g., lower limb ischemia (LLI). Thoracic endovascular aortic repair (TEVAR) represents the standard treatment for complicated TBAD; however, with respect to LLI, data is scant. The aim of this study was to investigate clinical and morphological outcomes in patients with complicated TBAD and LLI managed with a "TEVAR-first" policy. Between March 1997 and December 2021, 731 TEVAR-procedures were performed, including 106 TBAD-cases. Cases with TBAD + LLI were included in this retrospective analysis. Study endpoints were morphological/clinical success of TEVAR, regarding aortic and extremity-related outcome, including extremity-related adjunct procedures (erAP) during a median FU of 28.68 months. A total of 20/106 TBAD-cases (18.8%, 32-82 years, 7 women) presented with acute LLI (12/20 Rutherford class IIb/III). In 15/20 cases, true lumen-collapse (TLC) was present below the aortic bifurcation. In 16/20 cases, TEVAR alone resolved LLI. In the remaining four cases, erAP was necessary. A morphological analysis showed a relation between lower starting point and lesser extent of TLC and TEVAR success. No extremity-related reinterventions and only one major amputation was needed. The data strongly suggest that aTEVAR-first-strategy for treating TBAD with LLI is reasonable. Morphological parameters might be of importance to anticipate the failure of TEVAR alone.

Gene Expression Profiling in Abdominal Aortic Aneurysms.

Gene expression profiling of abdominal aortic aneurysms (AAA) indicates that chronic inflammatory responses, active matrix metalloproteinases, and degradation of the extracellular matrix components are involved in disease development and progression. This study investigates intra- and interpersonal RNA genome-wide expression profiling differences (Illumina HumanHT-12, BeadCHIP expression) of 24 AAA biopsies from 12 patients using a single gene and pathway (GeneOntology, GO enrichment) analysis. Biopsies were collected during open surgical AAA repair and according to prior finite element analysis (FEA) from regions with the highest and lowest wall stress. Single gene analysis revealed a strong heterogeneity of RNA expression parameters within the same and different AAA biopsies. The pathway analysis of all samples showed significant enrichment of genes from three different signaling pathways (integrin signaling pathway: fold change FC 1.63, p = 0.001; cholecystokinin receptor pathway: FC 1.60, p = 0.011; inflammation mediated by chemokine signaling pathway: FC 1.45, p = 0.028). These results indicate heterogeneous gene expression patterns within the AAA vascular wall. Single biopsy investigations do not permit a comprehensive characterization of activated molecular processes in AAA disease.

Inflammasomes in the Pathophysiology of Aortic Disease.

Aortic diseases comprise aneurysms, dissections, and several other pathologies. In general, aging is associated with a slow but progressive dilation of the aorta, along with increased stiffness and pulse pressure. The progression of aortic disease is characterized by subclinical development or acute presentation. Recent evidence suggests that inflammation participates causally in different clinical manifestations of aortic diseases. As of yet, diagnostic imaging and surveillance is mainly based on ultrasonography, computed tomography (CT), and magnetic resonance imaging (MRI). Little medical therapy is available so far to prevent or treat the majority of aortic diseases. Endovascular therapy by the introduction of covered stentgrafts provides the main treatment option, although open surgery and implantation of synthetic grafts remain necessary in many situations. Because of the risks associated with surgery, there is a need for identification of pharmaceutical targets interfering with the pathophysiology of aortic remodeling. The participation of innate immunity and inflammasome activation in different cell types is common in aortic diseases. This review will thus focus on inflammasome activities in vascular cells of different chronic and acute aortic diseases and discuss their role in development and progression. We will also identify research gaps and suggest promising therapeutic targets, which may be used for future medical interventions.

Midterm single-center results after endovascular aneurysm sealing reveal a high rate of stent graft migration, secondary aneurysm ruptures, and device-related reinterventions.

OBJECTIVE: To report procedural results and mid-term follow-up outcomes of patients treated with endovascular aneurysm sealing (EVAS) for abdominal aortic disease. METHODS: In this retrospective observational study, all patients treated with EVAS between March 2013 and January 2018 for abdominal aortic aneurysm (AAA) or abdominal penetrating aortic ulcer were included. The datasets included demographics, aneurysm morphology, and procedural and clinical surveillance outcomes. Furthermore, patients treated within the original instructions for use (IFU-group) were compared with patients treated outside the IFU (non-IFU-group) with regard to survival, reintervention-free survival, freedom from type I endoleak, and freedom from stent graft migration. RESULTS: Seventy patients were included (67 male; median age, 72.5 years). Sixty-five patients were treated for AAA and 5 patients for abdominal penetrating aortic ulcer. Sixty-nine cases were treated electively (98.6%). Technical success was achieved in 68 cases (97.1%). The median clinical follow-up was 50.5 months (interquartile range, 29.3-62.7 months) with a median computed tomography angiographic follow-up of 38.5 months (interquartile range, 17.1-60.2 months). There were five deaths during the study period (7.1%), four of which were aneurysm related (5.7%). Five secondary AAA ruptures were detected (7.1%). Overall, 25 of 70 patients (35.7%) underwent 35 reinterventions, mostly owing to thrombotic complications (18.6%), stent graft migration (17.1%), and type I endoleak (12.9%). Fifteen patients were treated outside of the IFU (non-IFU-group) (21.4%). The estimated reintervention-free survival for the entire cohort at 30 days and 1, 3, and 5 years was 94.3%, 88.5%, 72%, and 56.9%, respectively. Freedom from stent graft migration at 1, 3, and 5 years was 98.6%, 82.0%, and 47.3%, respectively. The estimated freedom from type I endoleak at 30 days and 1, 3, and 5 years in the IFU-group was 100%, 100%, 94.9% and, 91.1% and significantly different when compared with the non-IFU-group with 79.5%, 72.2%, 72.2%, and 72.2% (P = .012). CONCLUSIONS: Although the technical and initial results were satisfying, the mid-term results were disappointing. The enforcement of a close follow-up protocol for all patients treated with EVAS, especially vigilant for stent graft migration to prevent secondary type I endoleak and rupture, is strongly recommended.

Isolated femoral artery revascularisation with or without iliac inflow improvement - a less invasive surgical option in critical limb ischemia.

Background: Isolated femoral artery revascularisation (iFAR) represents a well-established surgical method in the treatment of peripheral arterial disease (PAD) involving common femoral artery disease. Data for iFAR in multilevel PAD are inconsistent, particularly in patients with critical limb ischemia (CLI). The aim of the study was to evaluate the outcome of iFAR in CLI regarding major amputation and reintervention and to identify associated risk factors for this outcome. Patients and methods: The data used have been derived from the German Registry of Firstline Treatment in Critical Limb Ischemia (CRITISCH). A total of 1200 patients were enrolled in 27 vascular centres. This sub-analysis included patients, which were treated with iFAR with/without concomitant iliac intervention. For detection of risk factors for the combined endpoint of major amputation and/or reintervention, selection of variables for multiple regression was conducted using stepwise forward/backward selection by Akaike's information criterion. Results: 95 patients were included (mean age: 72 years ± 10.82; 64.2% male). Of those, 32 (33.7%) participants reached the combined endpoint. Risk factor analysis revealed continued tobacco use (odds ratio [OR] 2.316, confidence interval [CI] 0.832-6.674), TASC D-lesion (OR: 2.293, CI: 0.869-6.261) and previous vascular intervention in the trial leg (OR: 2.720, CI: 1.037-7.381) to be associated with reaching the combined endpoint. Conclusions: iFAR provides a reasonable, surgical option to treat CLI. Lesion length (TASC D) seems to have a negative impact on outcome. Further research is required to better define the future role of iFAR for combined femoro-popliteal lesions in CLI - best in terms of a randomised controlled trial.

The C57Bl/6J mouse strain is more susceptible to angiotensin II-induced aortic aneurysm formation than C57Bl/6N.

BACKGROUND AND AIMS: Genetic variations between C57Bl/6 mouse substrains are highly relevant to the investigation of cardiovascular disease. We here assessed whether these variations have an impact on the incidence of abdominal aortic aneurysms (AAA) in C57Bl/6J and 6 N mice. METHODS: AAA were induced by subcutaneous infusion of 1500 ng/kg*min Angiotensin-II for four weeks in six-month-old male CB57Bl/6J and 6N mice. Aortic smooth muscle cells (VSMC) were isolated from untreated animals for in vitro analysis. RESULTS: C57Bl/6J mice are more susceptible to AAA formation (76.5% vs. 7.1%, p = 0.0002). C57Bl/6J VSMC expressed more pro-inflammatory molecules such as Nlrp3, Aim2 and NF-κB. Additionally, these cells presented significantly higher levels of NADP/NADPH and oxidative DNA modifications, as indicated by 8-OHdG-staining, compared to C57Bl/6N VSMC. CONCLUSIONS: In contrast to previous reports, we present evidence that six-month-old C57BL/6J, but not C57BL/6N mice develop AAA. In accordance with the deficiency of nicotinamide-nucleotide-transhydrogenase (Nnt), C57BL/6J VSMC displayed increased oxidative stress, oxidative DNA damage and a stronger inflammatory phenotype than C57BL/6N VSMC.

Inflammasome Targeted Therapy as Novel Treatment Option for Aortic Aneurysms and Dissections: A Systematic Review of the Preclinical Evidence.

Both aortic aneurysm and dissection are life threatening pathologies. In the lack of a conservative medical treatment, the only therapy consists of modifying cardiovascular risk factors and either surgical or endovascular treatment. Like many other cardiovascular diseases, in particular atherosclerosis, aortic aneurysm and dissection have a strong inflammatory phenotype. Inflammasomes are part of the innate immune system. Upon stimulation they form multi protein complexes resulting mainly in activation of interleukin-1ß and other cytokines. Considering the gathering evidence, that inflammasomes are decisively involved in the emergence and progression of aortic diseases, inflammasome targeted therapy provides a promising new treatment approach. A systematic review following the PRISMA guidelines on the current preclinical data regarding the potential role of inflammasome targeted drug therapy as novel treatment option for aortic aneurysms and dissections was performed. Included were all rodent models of aortic disease (aortic aneurysm and dissection) evaluating a drug therapy with direct or indirect inhibition of inflammasomes and a suitable control group with the use of the same aortic model without the inflammasome targeted therapy. Primary and secondary outcomes were incidence of aortic disease, aortic rupture, aortic related death, and the maximum aortic diameter. The literature search of MEDLINE (via PubMed), the Web of Science, EMBASE and the Cochrane Central Registry of Registered Trials (CENTRAL) resulted in 8,137 hits. Of these, four studies met the inclusion criteria and were therefore eligible for data analysis. In all of them, targeting of the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome effectively reduced the incidence of aortic disease and aortic rupture, and additionally reduced destruction of the aortic wall. Treatment strategies aiming at other inflammasomes could not be identified. In conclusion, inflammasome targeted therapies, more precisely targeting the NLRP3 inflammasome, have shown promising results in rodent models and deserve further investigation in preclinical research to potentially translate them into clinical research for the treatment of human patients with aortic disease. Regarding other inflammasomes, more preclinical research is needed to investigate their role in the pathophysiology of aortic disease. Protocol Registration: PROSPERO 2021 CRD42021279893, https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021279893.

Comparison of endovascular aneurysm sealing and repair with respect to contrast use and radiation in comparable patient cohorts.

BACKGROUND: Due to recent advances in endograft design and percutaneous access, technical success could be increased during endovascular aneurysm repair (EVAR). Beside EVAR, endovascular aneurysm sealing (EVAS) provides an alternative procedure to treat aneurysms. To compare the two methods, additional benchmark criteria should be evaluated: Screening time, dose area product (DAP), procedure time and contrast use. In this study these technical variables are analyzed for EVAS vs. EVAR in comparable patient cohorts. METHODS: It is a retrospective, single-center study. Only elective cases of infrarenal aortic aneurysms were included, all treated by the same surgeon (D.B.). Procedures were performed within the instructions for use without additional procedures. All operations were undertaken in a hybrid operating theatre. For EVAR, only the Medtronic Endurant® and the Gore C3 Excluder® were included. For EVAS the Nellix® from Endologix was used. RESULTS: Between 2012 and 2016, 67 patients were treated with EVAS and 40 with EVAR; of these 20 and 16 could be introduced into the study respectively. Median age was 73 and 72 years respectively (only men). The two groups were comparable in terms of BMI, GFR and ASA-status. Screening time was reduced for EVAS (10.6 vs. 14.5 min., P<0.01), while the DAP was not significantly different. Procedural time and contrast use were increased for EVAS (120 vs. 96 min., 120 vs. 79 mL, P<0.01). CONCLUSIONS: Especially the younger EVAS-procedure requires ongoing review in order to further reduce contrast agent. Reduced screening time for EVAS does not have a significant impact on radiation dose.

Vascular Biomaterial Banking in Academia.

BACKGROUND/PURPOSE: To establish a high-quality vascular biomaterial bank to serve vascular research teams and act as a basis for translational medicine. The aim was to collect and store material so that investigation into the pathogenesis of vascular disease would be possible employing methods based on histopathology and/or molecular biology. METHODS: The Vascular Biomaterialbank Heidelberg (VBBH) evolved as part of an established, partly accredited biobank complex at the University of Heidelberg (BioMaterialBank Heidelberg - BMBH). The BMBH provided infrastructure regarding legal and quality issues as well as safety, protocols for specimen collection, data management, and publication of results. Protocols were modified where necessary to accommodate specific needs of vascular tissue research. Correct identification of vascular biomaterial is controlled by certified vascular surgeons and pathologists at biobank entry and exit. Pseudonymized clinical data are attached to every specimen. RESULTS: The VBBH provides standardized operating procedures (SOP) regulating the request, processing, and delivery of material to researchers, as well as project tracking. Tissue samples for a research project are requested by filling out an online application form. Within 3-5 working days, a scientific board, including a member of the VBBH and a member of the BMBH, decide upon acceptance or rejection of the research project. Criteria determining acceptance include whether enough samples are available for the particular investigation and whether planned methods are judged adequate to successfully complete the research project. Through tracking of all ongoing studies involving specimens from the VBBH, methods for tissue conservation are continually being optimized. The VBBH platform has supported numerous high-ranking publications involving diverse medical departments and reflects a gain in translational medicine. CONCLUSIONS: SOPs and controls by certified specialists ensure the high quality of specimens obtained through the VBBH. Research performed by vascular surgeons can be facilitated by using the VBBH.

Necrotic cell debris induces a NF-κB-driven inflammasome response in vascular smooth muscle cells derived from abdominal aortic aneurysms (AAA-SMC).

Abdominal aortic aneurysm (AAA) is a multi-factorial progressive vascular disease with life-threatening complications. Increasing evidence suggests that smooth muscle cell (SMC) dysfunction and cell death contribute to dilatation and rupture of the aorta by inducing an inflammatory response. The exact mechanism of this response however, is incompletely understood. We here investigated in vitro the capacity of autologous necrotic cell debris (CD) to induce inflammasome components and inflammatory mediators in aortic SMC (AAA-SMC) isolated from patients with AAA undergoing surgical repair. AAA-SMCs were additionally primed with Interferon- γ (IFN-γ) before treatment with CD in order to mimic the proinflammatory status caused by higher IFN-γ concentrations that have been demonstrated in the wall of AAAs. Real-time RT-PCR revealed that CD significantly increased NLRP3 and IL1B mRNA expression in different SMC cultures within 6 h of exposure. Priming of the AAA-SMC with IFN-γ significantly increased expression of NLRP3, AIM2, IFI16 and CASP1 mRNAs, whereas IL1B mRNA was reduced. Additional exposure of IFN-γ-primed AAA-SMC to CD for 6-24 h, further augmented expression of AIM2, NLRP3, and Caspase-1 protein levels. Analysis of the SMC supernatants by ELISA revealed CD-induced release of the senescence-associated cytokines IL-6 and MCP-1 in native and IFN-γ-primed SMC, whereas no secretion of Interleukin-(IL) 1α and IL-1ß secretion were observed. Our results implicate a role of necrotic cell debris derived from dead neighboring cells in SMC dysfunction and in inflammatory response of AAA tissue.

Effect of metformin treatment in patients with type 2 diabetes with respect to glyoxalase 1 activity in atherosclerotic lesions.

BACKGROUND: The enzyme glyoxalase1 (GLO1) is the main opponent in the degradation of the reactive metabolite methylglyoxal (MG), which by glycation of macromolecules is involved in atherogenesis. Reduced GLO1-activity in atherosclerotic tissue is known to be associated with diabetes. It has been shown that treatment of patients with type 2 diabetes with metformin leads to increased GLO1-activity in peripheral-blood-cells. The aim of this study was to evaluate whether metformin treatment increases GLO1-activity in atherosclerotic lesions of patients with type 2 diabetes. PATIENTS AND METHODS: Patients with type 2 diabetes and carotid artery disease were included into the study prospectively. Type of diabetes-medication was documented upon admission along with demographic and clinical history. Using shock frozen endarterectomy-derived carotid artery plaques, GLO1-activity as well as protein expression was measured by a spectophotometric assay and western-blotting respectively. RESULTS: 33 patients (76 % male, mean age 71 years) were included into the study and were divided according to treatment with metformin or not (15 vs. 18 patients). GLO1-activity was increased by the factor 1.36 when treated with metformin - however, not significantly (0.86 vs. 0.63 U/mg, p = 0.056). Normalisation of GLO1-activity onto GLO1-expression level lead to a significant increase by more than twofold (8.48 vs. 3.85, p = 0.044) while GLO1-protein levels did not differ significantly. GLO1-activity correlated positively with increasing HbA1c, especially under metformin treatment. CONCLUSIONS: Treatment with metformin in patients with type 2 diabetes is associated with enhanced GLO1-activity in atherosclerotic lesions. Regarding the macro- and microvascular complications in these patients further studies are needed to gain more insight into the effect of metformin on the GLO/MG system.

Extended use of endovascular aneurysm sealing for ruptured abdominal aortic aneurysms.

Endovascular repair of abdominal aortic aneurysms (EVAR) is now an established treatment modality for suitable patients presenting with aneurysm rupture. EVAR for ruptured aneurysms reduces transfusion, mechanical ventilation, intensive care. and hospital stay when compared with open surgery. In the emergency setting, however, EVAR is limited by low applicability due to adverse clinical or anatomical characteristics and increased need for reintervention. In addition, ongoing bleeding from aortic side branches post-EVAR can cause hemodynamic instability, larger hematomas, and abdominal compartment syndrome. Endovascular aneurysm sealing, based on polymer filling of the aneurysm, has the potential to overcome some of the limitations of EVAR for ruptured aneurysms and to improve outcomes. Recent literature suggests that endovascular aneurysm sealing can be performed with early mortality similar to that of EVAR for ruptured aortic aneurysms, but experience is limited to a few centers and a small number of patients. The addition of chimney grafts can increase the applicability of endovascular aneurysm sealing in order to treat short-neck and juxtarenal aneurysms as an alternative to fenestrated endografts. Further evaluation of the technique, with larger longitudinal studies, is necessary before advocating wider implementation of endovascular aneurysm sealing in the emergency setting.

Reduced glyoxalase 1 activity in carotid artery plaques of nondiabetic patients with increased hemoglobin A1c level.

OBJECTIVE: Glyoxalase 1 (GLO1) is ubiquitously expressed in the cytosol of the cell and is the major opponent against the reactive metabolite methylglyoxal, which is involved in the development of atherosclerosis. Nondiabetic individuals with an increased hemoglobin A1c (HbA1c) level are at higher risk for development of cardiovascular diseases. As such, this study investigated whether there was an association between reduced GLO1 activity in atherosclerotic lesions of nondiabetic patients with an increased HbA1c level. METHODS: HbA1c level was determined in venous blood of patients with carotid artery disease. Protein level of GLO1 was measured in endarterectomy-derived carotid artery plaques by Western blotting. Activity was measured by spectrophotometric assay in the plaques as well as in the erythrocytes; GLO1 activity in erythrocytes was compared with that in a cohort of healthy individuals (n = 15; 33% men; average age, 60 years). RESULTS: There were 36 patients with carotid artery disease (69% men; average age, 69 years) included in this study and divided into two equal groups: group I, HbA1c < 5.7% (<39 mmol/mol); and group II, 5.7% ≤ HbA1c < 6.5% (39 mmol/mol ≤ HbA1c < 48 mmol/mol). GLO1 activity in carotid plaques was reduced by 29% in group II compared with group I (P = .048), whereas protein expression was unchanged (P = .25). Analysis of GLO1 activity in erythrocytes revealed no difference between the groups (P = .36) or in comparison to healthy controls (P = .15). Examination of clinical parameters showed an increased amount of patients with concomitant peripheral arterial disease in group II (44% vs 10%; P = .020). CONCLUSIONS: Reduction of GLO1 activity in atherosclerotic lesions of nondiabetic patients with increased HbA1c is associated with a functional involvement of this protective enzyme in atherogenesis. Systemic GLO1 activity seems to be independent of both HbA1c and localized atherosclerosis as it was unchanged between group I and group II as well as compared with healthy controls, respectively.

Current treatment strategies for ruptured abdominal aortic aneurysm.

BACKGROUND: Ruptured abdominal aortic aneurysm (rAAA) represents one of the most challenging emergencies in surgery. Open repair (OR) is associated with relevant morbidity and mortality and has not been reduced significantly over the last decade. The introduction of endovascular aneurysm repair (EVAR) and its meanwhile common use in the treatment of rAAA has raised the demand for randomised controlled trials (RCTs) in order to resolve a potential superiority of either OR or EVAR. PURPOSE: This review discusses the current treatment strategies in rAAA repair including diagnostics, peri-operative management and results of OR and EVAR, focussing on RCTs comparing both modalities. RESULTS: Thirty-day mortality after OR and EVAR shows no significant difference in published RCTs. In particular with respect to OR, 30-day mortality was much lower than anticipated throughout all RCTs ranging from 18 to 37 %. EVAR for rAAA resulted in reduced in-hospital stay. Limitations of all except one RCT are low patient recruitment and exclusion of haemodynamically unstable patients. CONCLUSIONS: OR and EVAR need to be provided for rAAA. Despite lacking evidence, EVAR is the first choice treatment in experienced high-volume vascular centres. Low mortality rates in all RCTs raise the question if aortic surgery should be centralised.

A Glyoxalase-1 Knockdown Does Not Have Major Short Term Effects on Energy Expenditure and Atherosclerosis in Mice.

Objective. Glyoxalase-1 is an enzyme detoxifying methylglyoxal (MG). MG is a potent precursor of advanced glycation endproducts which are regarded to be a key player in micro- and macrovascular damage. Yet, the role of Glo1 in atherosclerosis remains unclear. In this study, the effect of Glo1 on mouse metabolism and atherosclerosis is evaluated. Methods. Glo1 knockdown mice were fed a high fat or a standard diet for 10 weeks. Body weight and composition were investigated by Echo MRI. The PhenoMaster system was used to measure the energy expenditure. To evaluate the impact of Glo1 on atherosclerosis, Glo1(KD) mice were crossed with ApoE-knockout mice and fed a high fat diet for 14 weeks. Results. Glo1 activity was significantly reduced in heart, liver, and kidney lysates derived from Glo1(KD) mice. Yet, there was no increase in methylglyoxal-derived AGEs in all organs analyzed. The Glo1 knockdown did not affect body weight or body composition. Metabolic studies via indirect calorimetry did not show significant effects on energy expenditure. Glo1(KD) mice crossed to ApoE(-/-) mice did not show enhanced formation of atherosclerosis. Conclusion. A Glo1 knockdown does not have major short term effects on the energy expenditure or the formation of atherosclerotic plaques.

Type IIIb endoleak after thoracic endovascular aortic repair caused by endoanchor dislocation.

BACKGROUND: The aim of this study was to report the occurrence of a type IIIb endoleak after endovascular repair of a thoracic aortic aneurysm caused by endoanchor dislocation. CASE REPORT: An 84-year-old female patient underwent thoracic endovascular repair for aneurysmal disease of her thoracic aorta. The procedure included primary left subclavian artery revascularization and the placement of endoanchors to enhance fixation of the endograft within the aortic arch. Dislocation of one of the endoanchors resulted in a graft defect leading to a type IIIb endoleak and aortic diameter expansion. CONCLUSIONS: Endoanchors represent a promising adjunct in endovascular repair settings. However, their use requires careful procedure planning and special attention during follow-up.

Device Conformability and Morphological Assessment After TEVAR for Aortic Type B Dissection: A Single-Centre Experience with a Conformable Thoracic Stent-Graft Design.

BACKGROUND The aim of this study was to analyze device conformability in TEVAR of acute and chronic (a/c) type B aortic dissections (TBAD) using the Gore Conformable Thoracic Aortic Stent-graft (CTAG). MATERIAL AND METHODS From January 1997 to February 2014, a total of 90 out of 405 patients in our center received TEVAR for TBAD. Since November 2009, 23 patients (16 men; median age: 62 years) were treated with the CTAG. Indications were complicated aTBAD in 15 (65%) and expanding cTBAD in 8 (35%) patients. Primary endpoints were the assessment of device conformability by measuring the distance (D) from the radiopaque gold band marker (GM) at the proximal CTAG end to the inner curvature (IC) of the arch on parasagittal multiplanar reformations of CT angiography, as well as the evaluation of aortic diameter changes following TEVAR. Median follow-up was 13.3 months (range: 2 days to 35 months). RESULTS Primary and secondary success rates were 91.3% (21/23) and 95.6% (22/23), respectively. There was 1 type Ia endoleak, retrograde dissection or primary conversion was not observed. Median GM-IC-D was 0 mm (range: 0 mm to 10 mm). GM-IC-D was associated with zone 2 placement compared to zone 3 (P=0.036). There was no association between GM-IC-D formation and arch type. In aTBAD cases the true lumen significantly increased after TEVAR (P=0.017) and the false lumen underwent shrinkage (P=0.025). In cTBAD patients the false lumen decreased after TEVAR (P=0.036). CONCLUSIONS The CTAG shows favorable conformability and wall apposition in challenging arch pathologies such as TBAD.

Cyclic mechanical strain induces TGFß1-signalling in dermal fibroblasts embedded in a 3D collagen lattice.

Many tissues are constantly exposed to mechanical stress, e.g. shear stress in vascular endothelium, compression forces in cartilage or tensile strain in the skin. Dermal fibroblasts can differentiate into contractile myofibroblasts in a process requiring the presence of TGFß1 in addition to mechanical load. We aimed at investigating the effect of cyclic mechanical strain on dermal fibroblasts grown in a three-dimensional environment. Therefore, murine dermal fibroblasts were cultured in collagen gels and subjected to cyclic tension at a frequency of 0.1 Hz (6 cycles/min) with a maximal increase in surface area of 10 % for 24 h. This treatment resulted in a significant increase in active TGFß1 levels, leaving the amount of total TGFß1 unaffected. TGFß1 activation led to pSMAD2-mediated transcriptional elevation of downstream mediators, such as CTGF, and an auto-induction of TGFß1, respectively.