Publications by authors named "Wolf Eilenberg"

19 Publications

  • Page 1 of 1

Abdominal aortic aneurysm and virus infection: a potential causative role for cytomegalovirus infection?

J Med Virol 2021 Feb 25. Epub 2021 Feb 25.

Department of Surgery, Division of Vascular Surgery, Medical University of Vienna, Vienna, Austria.

An abdominal aortic aneurysm (AAA) is a multifactorial disease with a variety of genetic and environmental risk factors, but the exact mechanism of AAA formation and progression is still not well understood. The present study investigated the frequency of cytomegalovirus (CMV), Epstein-Barr virus (EBV), and papillomavirus types 6 and 11 (HPV6 and HPV11), their impact on clinical manifestations of cardiovascular diseases, and their possible association with inflammation in patients with AAA and healthy volunteers. Genotyping of CMV UL75, EBV LMP-1, and HPV6 and HPV11 E6 was performed by polymerase chain reaction (PCR), while the viral DNA loads were measured by quantitative real-time PCR (qRT-PCR). Cytokine levels were determined by enzyme-linked immunosorbent assays (ELISAs). The CMV UL75 was detected more frequently in the blood of patients with AAA than in the blood of healthy volunteers (32.7% vs. 6.3%, p < 0.0001). Neither EBV LMP-1 nor HPV6 E6 was found in blood and aortic wall biopsies, while the HPV11 E6 was detected in 36.4% of AAA walls. The CMV infection in patients with AAA was associated with an increased risk of hypertension and coronary artery disease (CAD) (OR 9.057; 95% CI: 1.141 - 71.862, p = 0.037; OR 2.575; 95% CI: 1.002 - 6.615, p = 0.049, respectively). Additionally, CMV-infected patients with AAA had higher TNF-α levels compared with non-infected subjects (p = 0.017). Our findings suggest that CMV infection can stimulate local inflammation in the aorta but is not a direct cause of most abdominal aortic aneurysms. This article is protected by copyright. All rights reserved.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jmv.26901DOI Listing
February 2021

Histone citrullination as a novel biomarker and target to inhibit progression of abdominal aortic aneurysms.

Transl Res 2021 Feb 9. Epub 2021 Feb 9.

Department of General Surgery: Division of Vascular Surgery, Medical University of Vienna, Vienna, Austria. Electronic address:

Neutrophil extracellular traps (NETs) have been implicated in the pathogenesis of abdominal aortic aneurysms (AAAs). This study has addressed the notion that NET components might serve as AAA biomarkers or novel targets of AAA therapy. Thus, parameters of neutrophil activation and NET formation were measured in plasma. Their diagnostic marker value was explored in 41 AAA patients and 38 healthy controls. The NET parameter citrullinated histone H3 (citH3) was then validated in 63 AAA patients and 63 controls matched for cardiovascular disease. The prognostic marker potential was investigated in 54 observation periods of AAA growth over 6 months. NETs were further assessed in conditioned medium and sections of aortic tissue. CitH3 was found to be increased in blood (median 362 vs 304 ng/mL, P = 0.004) and aortic tissue (50 vs 1.5 ng/mg, P < 0.001) of AAA patients compared to healthy controls and accumulated in the intraluminal thrombus (629 ng/mg). The diagnostic potential of citH3 ranged at 0.705 area under the ROC curve (AUROC) and was validated with the independent sample set. Furthermore, plasma citH3 predicted AAA growth over the next 6 months (AUROC: 0.707, P = 0.015) and dropped significantly after surgical aneurysm repair. In an angiotensin II - based mouse model of experimental AAA, an inhibitor of histone citrullination was applied to block NET formation and AAA progression. Of note, further growth of an established aneurysm was prevented in mice treated with the NET inhibitor (P = 0.040). In conclusion, histone citrullination represents a promising AAA biomarker and potential therapeutic target to control disease progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.trsl.2021.02.003DOI Listing
February 2021

Neutrophil Extracellular Traps and Their Implications in Cardiovascular and Inflammatory Disease.

Int J Mol Sci 2021 Jan 8;22(2). Epub 2021 Jan 8.

Division of Vascular Surgery and Surgical Research Laboratories, Department of Surgery, Medical University of Vienna, General Hospital of Vienna, 1090 Vienna, Austria.

Neutrophils are primary effector cells of innate immunity and fight infection by phagocytosis and degranulation. Activated neutrophils also release neutrophil extracellular traps (NETs) in response to a variety of stimuli. These NETs are net-like complexes composed of cell-free DNA, histones and neutrophil granule proteins. Besides the evolutionarily conserved mechanism to capture and eliminate pathogens, NETs are also associated with pathophysiological processes of various diseases. Here, we elucidate the mechanisms of NET formation and their different implications in disease. We focused on autoinflammatory and cardiovascular disorders as the leading cause of death. Neutrophil extracellular traps are not only present in various cardiovascular diseases but play an essential role in atherosclerotic plaque formation, arterial and venous thrombosis, as well as in the development and progression of abdominal aortic aneurysms. Furthermore, NETosis can be considered as a source of autoantigens and maintains an inflammatory milieu promoting autoimmune diseases. Indeed, there is further need for research into the balance between NET induction, inhibition, and degradation in order to pharmacologically target NETs and their compounds without impairing the patient's immune defense. This review may be of interest to both basic scientists and clinicians to stimulate translational research and innovative clinical approaches.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms22020559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828090PMC
January 2021

Polymorphisms in the IL-6 and TNF-α gene are associated with an increased risk of abdominal aortic aneurysm.

Int J Cardiol 2021 Apr 6;329:192-197. Epub 2021 Jan 6.

Department of Surgery, Division of Vascular Surgery, Medical University of Vienna, Vienna, Austria.

Background: An abdominal aortic aneurysm (AAA) is a complex disease of the aging population that is associated with inflammation and the cellular immune response. To investigate the influence of interleukin (IL)-6 and tumor necrosis factor (TNF)-α single nucleotide polymorphisms (SNPs) on the risk of AAA formation and progression, the frequency of AAA and its associated risk factors were determined.

Method: Four SNPs in the IL-6 (-174G/C, rs1800795; -572G/C, rs1800796) and TNF-α (-238G/A, rs361525; -308G/A, rs1800629) genes were studied by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in patients with AAA and healthy volunteers. The mRNA expression and plasma IL-6 and TNF-α levels were also determined.

Results: A mutation detected in at least one allele of the IL-6 -174G/C SNP was associated with a 2-fold increased risk of AAA occurrence (OR: 2.08; 95% CI: 1.15-3.76; p = 0.014, in the dominant model). An increased risk of AAA incidence among heterozygous carriers of the TNF-α - 308G/A genotype was observed (OR: 2.06; 95% CI: 1.17-3.62; p = 0.011, in the overdominant model). The wild-type genotypes of the IL-6 -174G/C and the TNF-α -308G/A SNPs coexisted more frequently in healthy subjects than in AAA patients and was associated with decreased risk of AAA (p < 0.001). Moreover, elevated levels of IL-6 and TNF-α were associated with an increased risk of hypertension (p < 0.001 and p = 0.022, respectively).

Conclusions: The IL-6 -174G/C and the TNF-α -238G/A gene polymorphisms are associated with an increased risk of abdominal aortic aneurysm development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijcard.2020.12.051DOI Listing
April 2021

Silent Brain Infarction After Endovascular Arch Procedures: Preliminary Results from the STEP Registry.

Eur J Vasc Endovasc Surg 2021 02 22;61(2):239-245. Epub 2020 Dec 22.

Aortic Centre, Hôpital Marie Lannelongue, Groupe Hospitalier Paris Saint Joseph, Université Paris Saclay, Paris, France. Electronic address:

Objective: Few data exist concerning the rate of silent cerebral ischaemic events following endovascular treatment of the aortic arch. The objective of this work was to quantify these lesions using the STEP registry (NCT04489277).

Methods: This multicentre retrospective cohort study included consecutive patients treated with an aortic endoprosthesis deployed in Ishimaru zone 0-3 and brain diffusion weighted magnetic resonance imaging (DW-MRI) within seven days following the procedure. DW-MRI was performed to identify the location and number of new silent brain infarctions (SBI). All endografts were carbon dioxide flushed prior to implantation.

Results: The study population included 91 patients (mean age, 69 years; men, 64%) from two academic centres treated between September 2018 and January 2020. The procedure was elective in 71 patients (78%). The treatment was performed for a dissection, degenerative aneurysm, or other aortic disease in 44 (49%), 34 (37%), and 13 (14%) patients, respectively. Endografts were deployed in zone 0, 1, 2 or 3 in 23 (25%), 10 (11%), 47 (52%), and 11 (12%) patients, respectively. Endografts were branched (25%), fenestrated (17%), or tubular (58%). At 30 days, there were no deaths or clinical strokes. On cerebral DW-MRI, a total of 245 SBI were identified in 45 patients (50%). Lesions were in the left hemisphere in 63% of the patients (153/245), predominantly in the middle territory (94/245). Deployment in zone 0-1 (p = .026), placement of a branched or fenestrated endograft (p = .038), a proximal endoprosthesis diameter ≥ 40 mm (p = .038), and an urgent procedure (p = .005) were significantly associated with the presence of SBI on univariable analysis, while urgent procedure was found to be an independent predictor on multivariable analysis (binary logistic regression) (p = .002).

Conclusion: SBI following endovascular repair of the aortic arch is frequent, although there were no clinical strokes. Innovative strategies to reduce the risk of embolisation need to be developed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejvs.2020.11.021DOI Listing
February 2021

Complement Factor C5a Is Increased in Blood of Patients with Abdominal Aortic Aneurysm and Has Prognostic Potential for Aneurysm Growth.

J Cardiovasc Transl Res 2020 Dec 17. Epub 2020 Dec 17.

Department of Surgery: Division of Vascular Surgery and Surgical Research Laboratories, Medical University of Vienna, Vienna General Hospital, Vienna, Austria.

In this observational case-control study, circulating levels of complement factors C3a and C5a and leukotriene B4 (LTB4) were analysed in abdominal aortic aneurysm (AAA) patients regarding their association with diagnosis and prognosis. Serum C5a was significantly raised in AAA patients compared to healthy controls-median 84.5 ng/ml (IQR = 37.5 ng/ml) vs. 67.7 ng/ml (IQR = 26.2 ng/ml), p = 0.007-but was not elevated in patients with athero-occlusive disease. Serum C5a levels correlated significantly with the increase in maximum AAA diameter over the following 6 months (r = 0.319, p = 0.021). The median growth in the lowest quartile of C5a (< 70 ng/ml) was 50% less compared to the highest C5a quartile (> 101 ng/ml): 1.0 mm/6 months (IQR = 0.8 mm) vs. 2.0 mm/6 months (IQR = 1.5 mm), p = 0.014. A log-linear mixed model predicted AAA expansion based on current diameter and C5a level. To our knowledge, this is the first study linking complement activation, in particular C5a serum level, with AAA progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12265-020-10086-5DOI Listing
December 2020

Novel prefabricated bovine pericardial grafts as alternate conduit for septic aortoiliac reconstruction.

J Vasc Surg 2020 Dec 2. Epub 2020 Dec 2.

Division of Vascular Surgery, Department of General Surgery, Medical University of Vienna, Vienna, Austria. Electronic address:

Objective: Infection of prosthetic aortic grafts represents a serious complication with high morbidity and mortality. Replacement with autologous material is recommended; however, in its absence, biological material should be favored. In the present retrospective cohort study, we evaluated the short- and mid-term results with the use of commercially available prefabricated bovine pericardium grafts (BPGs) used for the management of aortic graft infection or aortic reconstructive surgery in the presence of systemic infection.

Methods: We performed a retrospective analysis of patients in whom BPGs had been used for aortic reconstruction at two vascular centers. Prefabricated vascular pericardium grafts were preferred over other biological reconstruction techniques for selected cases. Comorbidities, procedure-related details, perioperative morbidity, clinical outcomes, and mortality were analyzed.

Results: From 2014 to 2019, 21 patients had received BPGs at two Austrian vascular centers. Their median age was 63 years (interquartile range [IQR], 55-71 years), the patients were predominantly male (76%), and the median body mass index was 25.3 kg/m (IQR, 21.7-27.3 kg/m). The major comorbidities included arterial hypertension, peripheral artery disease, smoking, and chronic pulmonary disease. The indications for surgery were vascular graft or endograft infection in 62% and aortic reconstruction in the presence of systemic infection in 38%. Three patients (14%) had aortoenteric fistulas. Surgery was technically successful in all cases. The median follow-up was 21.6 months (IQR, 6.0-34.6 months). The 30-day mortality was 9.5%. The 1- and 2-year overall survival was 84% and 75%, respectively. Of the 21 patients, 89% had remained free of recurrent infection. One of the two reinfections had resolved after treatment of the underlying focus. At 2 years, the primary and assisted primary patency rates were 86% and 94%, respectively. No limbs were lost during follow-up.

Conclusions: Prefabricated BPGs represent a promising alternative for the management of aortic graft infections and aortoiliac reconstruction in the presence of systemic infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jvs.2020.11.028DOI Listing
December 2020

Comparison of transfemoral versus upper extremity access to antegrade branches in branched endovascular aortic repair.

J Vasc Surg 2020 Nov 26. Epub 2020 Nov 26.

German Aortic Center, Department of Vascular Medicine, University Heart and Vascular Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany. Electronic address:

Objective: We studied the outcomes of transfemoral access (TFA) vs upper extremity access (UEA) for branched endovascular aortic repair (BEVAR).

Methods: From January 2016 to October 2019, 152 consecutive patients underwent BEVAR under general anesthesia at a single institution. In 2018, an alternative approach to the antegrade branches using TFA compared with conventional UEA was introduced. The cohort was divided into TFA and UEA groups according to the access approach. The end points were technical success, adverse events (including perioperative stroke/transient ischemic attack), access complications, operation time, and radiation exposure.

Results: The TFA group included 60 patients (63% male; median age, 71 years; interquartile range [IQR], 65-76 years). The UEA group included 92 patients (67% male; median age, 73 years; IQR, 66-78 years). The number of target vessels (TVs) was similar in both groups (median, 4.0 TVs per procedure; range, 1-7 TVs for both). Technical success was greater in the TFA group (60 of 60 patients; 209 of 209 TVs) than in the UEA group (87 of 92 patients; 334 of 346 TVs; P < .01). The fluoroscopy time (median, 69 minutes; IQR, 48-87 minutes; vs 88 minutes; IQR, 65-104 minutes; P = .39) and contrast agent volume (median, 141 mL; IQR, 123-165 mL; vs median, 130 mL; IQR, 101-157 mL; P = .34) were similar in both groups. The radiation exposure (221 Gy × cm; IQR, 138-406 Gy × cm; vs median, 255 Gy × cm; IQR, 148-425 Gy × cm; P = .05) was lower and the operation time (median, 300 minutes; IQR, 240-356 minutes; vs median, 364 minutes; IQR, 290-475 minutes; P = .01) was shorter in the TFA group. Brachial access complications (0 of 60 vs 3 of 92 patients) and perioperative strokes/transient ischemic attacks (0 of 60 vs 8 of 92 patients) only occurred in the UEA group (P = .018).

Conclusions: The use of TFA to catheterize antegrade branches was associated with a lower rate of complications in the present study and has become our preferred approach for BEVAR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jvs.2020.11.020DOI Listing
November 2020

Neutrophil Extracellular Trap Degradation by Differently Polarized Macrophage Subsets.

Arterioscler Thromb Vasc Biol 2020 09 16;40(9):2265-2278. Epub 2020 Jul 16.

From the Division of Cardiology, Department of Medicine II (P. Haider, J.B.K.-P., J.M., M.R., C.K., W.S.S., C.H., J.W., P. Hohensinner), Medical University of Vienna, Austria.

Objective: Macrophages are immune cells, capable to remodel the extracellular matrix, which can harbor extracellular DNA incorporated into neutrophil extracellular traps (NETs). To study the breakdown of NETs we studied the capability of macrophage subsets to degrade these structures in vitro and in vivo in a murine thrombosis model. Furthermore, we analyzed human abdominal aortic aneurysm samples in support of our in vitro and in vivo results. Approach and Results: Macrophages were seeded onto blood clots or isolated NETs and polarized. All macrophages were capable to degrade NETs. For initial breakdown, macrophages relied on extracellular deoxyribonucleases. Proinflammatory polarization enhanced NET degradation. The boost in degradation was because of increased macropinocytosis, as inhibition by imipramine diminished their NET breakdown. Inhibition of macropinocytosis in a murine thrombosis model led to increased NET burden and reduced thrombus resolution in vivo. When analyzing abdominal aortic aneurysm samples, macrophage density furthermore corresponded negatively with the amount of local NETs in the intraluminal thrombi as well as in the vessel wall, as increased macrophage density was associated with a reduction in NET burden.

Conclusions: We provide evidence that macrophages degrade NETs by extracellular predigestion and subsequent uptake. Furthermore, we show that proinflammatory macrophages increase NET degradation through enhanced macropinocytosis, priming them for NET engulfment. Based on our findings, that inhibition of macropinocytosis in mice corresponded to increased NET amounts in thrombi and that local macrophage density in human abdominal aortic aneurysm is negatively associated with surrounding NETs, we hypothesize, that macrophages are able to degrade NETs in vivo.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/ATVBAHA.120.314883DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7447175PMC
September 2020

Vascular Surgery in Unreal Times.

Eur J Vasc Endovasc Surg 2020 08 28;60(2):167-168. Epub 2020 Jun 28.

Aortic Centre, Hopital Marie Lannelongue, Groupe Hospitalier Paris Saint Joseph, Universite Paris Saylay, Paris, France.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejvs.2020.05.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7320915PMC
August 2020

Inverse probability of treatment analysis of open vs endovascular repair in ruptured infrarenal aortic aneurysm - Cohort study.

Int J Surg 2020 Aug 15;80:218-224. Epub 2020 Jun 15.

Department of Surgery, Division of Vascular Surgery, Medical University of Vienna, Austria. Electronic address:

Background: To compare open repair (OR) with EVAR for the management of ruptured infrarenal abdominal aortic aneurysms (RAAA) in a cohort study over a time period of 15 years with inverse probability of treatment weights.

Material And Methods: From 2000/01 through 2015/12 136 patients were treated for RAAA, 98 (72.1%) underwent OR, 38 (27.9%) were treated with EVAR. Thirty-day and long-term mortality (survival) were analyzed in this IRB-approved retrospective cohort study. Treatment modalities were compared using inverse probability of treatment weights to adjust for imbalances in demographic data and risk factors.

Results: EVAR patients were older (75.11 ± 7.17 vs 69.79 ± 10.24; p=0.001). There was no statistical difference in gender, hypertension, COPD, CAD, or diabetes. GFR was significantly higher in OR patients (71.4 ± 31.09 vs. 53.68 ± 25.73). Postoperative dialysis was required more frequently in EVAR patients: 11% vs. 2% (p = 0.099). In the OR group, adjusted cumulative survival was 70.4% (61.1, 81.1) at 30 days, 47.0% (37.1, 59.6) at one year and 38.3% (28.6, 51.3) at 5 years. In the EVAR group the corresponding numbers were 77.0% (67.7, 87.5), 67.5% (57.0, 80.0) and 41.7% (30.4, 57.4), respectively.

Conclusion: There is evidence for EVAR patients exhibiting a benefit in one-year survival, while patients treated with OR may have more favorable long-term survival given they survive for at least one year. Herein we provide a statistically rigorous comparison of OR and EVAR in short and long-term outcomes with up to 15 years of follow-up.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijsu.2020.05.090DOI Listing
August 2020

2029C/T and 1377C/T and -7C/A Polymorphisms Are Associated with the Occurrence of Abdominal Aortic Aneurysm.

J Immunol 2020 06 13;204(11):2900-2909. Epub 2020 Apr 13.

Division of Vascular Surgery, Department of Surgery, Medical University of Vienna, A-1090 Vienna, Austria.

TLRs are a family of signaling sensors that play a crucial role in the host immune response and are involved in the modulation of inflammatory processes. To study their contribution to abdominal aortic aneurysm (AAA) formation and development, we determined the frequency of , , , and single-nucleotide polymorphisms (SNPs) and investigated the association between polymorphisms and the risk of AAA incidence. A total of 104 patients with AAAs and 112 healthy, unrelated volunteers were screened for the presence of (2029C/T and 2258G/A), (1377C/T, 1234C/T, and -7C/A), (896A/G, 1196C/T, and 3266G/A), and (-1237T/C, -1486T/C, 1174G/A, and 2848C/T) SNPs by using PCR-RFLP analysis. The heterozygous genotype of the 2029C/T SNP was more common in patients with AAA than in healthy subjects ( < 0.0001) and was associated with at least an 8-fold increased risk of AAA incidence ( < 0.001). The wild-type genotype of the -7C/A SNP was associated with a 3-fold increased risk of hypertension ( = 0.026). The heterozygous genotype 1377C/T and -7C/A SNPs were less common in patients with AAA than in healthy subjects ( < 0.0001 and = 0.0004, respectively) and were associated with a decreased risk of AAA occurrence ( < 0.001 and = 0.0012, respectively). No relation to AAA risk was found for SNPs. Heterozygous genotypes of the 2029C/T and 1377C/T and -7C/A SNPs may serve as genetic biomarkers of AAA incidence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4049/jimmunol.1901014DOI Listing
June 2020

Neutrophil Gelatinase Associated Lipocalin (NGAL) for Identification of Unstable Plaques in Patients with Asymptomatic Carotid Stenosis.

Eur J Vasc Endovasc Surg 2019 Jun 1;57(6):768-777. Epub 2019 Jun 1.

Department of Surgery, Division of Vascular Surgery, Medical University of Vienna, Austria. Electronic address:

Objective: Neutrophil gelatinase associated lipocalin (NGAL) and matrix metalloproteinase (MMP)-9/NGAL complex were investigated in asymptomatic patients with carotid artery stenosis including gender specific differences aiming at vulnerable plaques prone to embolisation.

Methods: Serum NGAL and MMP-9/NGAL levels were analysed in 83 patients with asymptomatic carotid artery stenosis. Pre-operative ultrasound and post-endarterectomy histology of carotid atherosclerotic lesions were evaluated.

Results: Patients with vulnerable plaques, as determined by ultrasound (plaques with decreased echogenicity) and histological analysis (type VI according to the classification of the American Heart Association), displayed the highest levels of NGAL and MMP-9/NGAL complex (p = .0003 and p = .0078, respectively). Grade VI plaques were primarily detected in patients with "soft" plaques (12 type VI plaques in 25 patients), but also in patients with mixed (four of 19) and calcified (three of 39) plaques according to ultrasound. Higher grade carotid artery stenosis (≥90%) was not associated with elevated NGAL levels. The receiver operating characteristic curve analysis detecting grade VI lesions yields an area under the curve (AUC) = 0.85, with respect to soft plaque on ultrasound the AUC = 0.86. There were no gender specific differences in levels of NGAL 80.9 (37.7) ng/mL in women vs. 76.7 (36.3) ng/mL in men, p = .607) nor of MMP-9/NGAL 33.0 (18.2-55.5) ng/mL in women vs. 36.7 (20.2-54.0) ng/mL in men, p = .969. Likewise, there were no gender associated differences in vulnerable plaque characteristics: either for grade VI plaques (17.9% vs. 27.3%, p = .582) or for the presence of soft plaques as evaluated by ultrasound (35.9% vs. 25%, p = .503).

Conclusion: Circulating NGAL and MMP-9/NGAL are significantly increased in asymptomatic patients with vulnerable carotid atherosclerotic plaques independent of gender. Accordingly, serum NGAL may be proposed as a valuable biomarker for the detection of unstable carotid plaques in asymptomatic patients, who can then be selected for early carotid endarterectomy or stenting.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejvs.2018.12.029DOI Listing
June 2019

CD46 knock-out using CRISPR/Cas9 editing of hTERT immortalized human cells modulates complement activation.

PLoS One 2019 8;14(4):e0214514. Epub 2019 Apr 8.

Evercyte GmbH, Vienna, Austria.

The kidney is especially sensitive to diseases associated with overactivation of the complement system. While most of these diseases affect kidney glomeruli and the microvasculature, there is also evidence for tubulointerstitial deposition of complement factors. Complement inactivating factors on cell membranes comprise CD55, CD59 and CD46, which is also termed membrane cofactor protein (MCP). CD46 has been described as localized to glomeruli, but especially also to proximal tubular epithelial cells (RPTECs). However, human cell culture models to assess CD46 function on RPTECs are still missing. Therefore, we here performed gene editing of RPTEC/TERT1 cells generating a monoclonal CD46-/- cell line that did not show changes of the primary cell like characteristics. In addition, factor I and CD46-mediated cleavage of C4b into soluble C4c and membrane deposited C4d was clearly reduced in the knock-out cell line as compared to the maternal cells. Thus, human CD46-/- proximal tubular epithelial cells will be of interest to dissect the roles of the epithelium and the kidney in various complement activation mediated tubulointerstitial pathologies or in studying CD46 mediated uropathogenic internalization of bacteria. In addition, this gives proof-of-principle, that telomerized cells can be used in the generation of knock-out, knock-in or any kind of reporter cell lines without losing the primary cell characteristics of the maternal cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0214514PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6453361PMC
December 2019

A Novel Diagnostic and Prognostic Score for Abdominal Aortic Aneurysms Based on D-Dimer and a Comprehensive Analysis of Myeloid Cell Parameters.

Thromb Haemost 2019 May 1;119(5):807-820. Epub 2019 Mar 1.

Division of Vascular Surgery and Surgical Research Laboratories, Department of Surgery, Medical University of Vienna, Vienna General Hospital, Vienna, Austria.

The pathogenesis of abdominal aortic aneurysm (AAA) involves a central component of chronic inflammation which is predominantly mediated by myeloid cells. We hypothesized that the local inflammatory activity may be reflected in systemic alterations of neutrophil and monocyte populations as well as in soluble factors of myeloid cell activation and recruitment. To establish their marker potential, neutrophil and monocyte sub-sets were measured by flow cytometry in peripheral blood samples of 41 AAA patients and 38 healthy controls matched for age, sex, body mass index and smoking habit. Comparably, circulating factors reflecting neutrophil and monocyte activation and recruitment were assayed in plasma. Significantly elevated levels of CD16+ monocytes, activated neutrophils and newly released neutrophils were recorded for AAA patients compared with controls. In line, the monocyte chemoattractant C-C chemokine ligand 2 and myeloperoxidase were significantly increased in patients' plasma. The diagnostic value was highest for myeloperoxidase, a mediator which is released by activated neutrophils as well as CD16+ monocytes. Multivariable regression models using myeloid activation markers and routine laboratory parameters identified myeloperoxidase and D-dimer as strong independent correlates of AAA. These two biomarkers were combined to yield a diagnostic score which was subsequently challenged for confounders and confirmed in a validation cohort matched for cardiovascular disease. Importantly, the score was also found suited to predict rapid disease progression. In conclusion, D-dimer and myeloperoxidase represent two sensitive biomarkers of AAA which reflect distinct hallmarks (thrombus formation and inflammation) of the pathomechanism and, when combined, may serve as diagnostic and prognostic AAA score warranting further evaluation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0039-1679939DOI Listing
May 2019

Preoperative ultrasound improves patency and cost effectiveness in arteriovenous fistula surgery.

J Vasc Surg 2019 02 9;69(2):526-531. Epub 2018 Oct 9.

Division of Transplantation, Department of Surgery, Medical University of Vienna, Vienna, Austria.

Objective: We aimed to compare routine preoperative color-coded duplex ultrasound (DUS) to clinical examination (CE) alone in surgery for arteriovenous fistula (AVF) with special emphasis on long-term outcomes and cost effectiveness.

Methods: All patients undergoing an AVF formation or revision between January 1, 2011, and December 31, 2016, at our tertiary referral center were subject to analysis. Routine DUS was performed in 114 patients and CE alone in 217 patients. Primary and secondary patency, the need for revision or reintervention to obtain patency, and individual as well as overall costs were analyzed.

Results: Primary patency rate was higher in AVF after DUS compared with CE alone at 62% vs 26% (P < .05), respectively. Patients receiving DUS had significantly lower rates of revision and revisions per patient when compared with CE (25.4% vs 59.4% [P < .0001]; 0.36 ± 0.71 vs 1.06 ± 1.55 [P < .0001], respectively). Costs per patient were significantly lower in the DUS group compared with CE at 4074€ vs 6078€ (P < .0001).

Conclusions: We were able to show that patients receiving preoperative DUS showed higher patency rates and needed fewer revisions. Standard preoperative ultrasound examination is an easy tool to improve outcomes and cost effectiveness in AVF surgery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jvs.2018.05.217DOI Listing
February 2019

NGAL and MMP-9/NGAL as biomarkers of plaque vulnerability and targets of statins in patients with carotid atherosclerosis.

Clin Chem Lab Med 2017 Nov;56(1):147-156

.

Background: Neutrophil gelatinase associated lipocalin (NGAL) is expressed in atherosclerotic lesions and was recently implicated in the pathogenesis of cardiovascular pathologies. Statins are known to exert stabilizing effects on atherosclerotic plaque. The aims of our study were (1) to investigate the association of serum NGAL and metalloproteinase (MMP)-9/NGAL complex with the vulnerability of the atherosclerotic plaque, and (2) to reveal the effects of statin treatment on circulating NGAL and MMP-9/NGAL levels in patients with carotid artery stenosis.

Methods: We examined the levels of NGAL and MMP-9/NGAL in blood samples from 136 patients with carotid artery stenosis by specific enzyme-linked immunosorbent assays.

Results: Patients with vulnerable plaques, as determined by ultrasound (plaques with decreased echogenicity) and histological analysis (type VI according to the classification of American Heart Association [AHA]), displayed the highest levels of NGAL (both p<0.0001) and MMP-9/NGAL complex (p=0.0004 and p=0.004, respectively). Moreover, patients with symptomatic carotid atherosclerosis had significantly higher NGAL levels compared to asymptomatic patients (p=0.0007). The statin-treated group (n=108) demonstrated lower NGAL (73.9 vs. 128.0 μg/L, p<0.0001) and MMP-9/NGAL (28.9 vs. 40.6 μg/L, p=0.046) as compared to the non-statin group (n=28). Furthermore, in multivariate regression analysis NGAL, but not MMP-9/NGAL levels, were independently associated with symptomatic carotid artery stenosis. In addition, statin treatment was independently associated with lower NGAL levels.

Conclusions: Circulating NGAL and MMP-9/NGAL are associated with plaque vulnerability in patients with carotid artery stenosis. Statin treatment could contribute to plaque stabilization by reducing circulating NGAL and MMP-9/NGAL levels.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1515/cclm-2017-0156DOI Listing
November 2017

The Abdominal Aortic Aneurysm and Intraluminal Thrombus: Current Concepts of Development and Treatment.

Front Cardiovasc Med 2015 26;2:19. Epub 2015 May 26.

Department of Surgery, Medical University of Vienna , Vienna , Austria.

The pathogenesis of the abdominal aortic aneurysm (AAA) shows several hallmarks of atherosclerotic and atherothrombotic disease, but comprises an additional, predominant feature of proteolysis resulting in the degradation and destabilization of the aortic wall. This review aims to summarize the current knowledge on AAA development, involving the accumulation of neutrophils in the intraluminal thrombus and their central role in creating an oxidative and proteolytic environment. Particular focus is placed on the controversial role of heme oxygenase 1/carbon monoxide and nitric oxide synthase/peroxynitrite, which may exert both protective and damaging effects in the development of the aneurysm. Treatment indications as well as surgical and pharmacological options for AAA therapy are discussed in light of recent reports.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcvm.2015.00019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4671358PMC
December 2015

Gastro-oesophageal reflux disease in type 2 diabetics: symptom load and pathophysiologic aspects - a retro-pro study.

BMC Gastroenterol 2013 Aug 23;13:132. Epub 2013 Aug 23.

Background: Information about gastro-oesophageal reflux disease (GERD) in patients with Diabetes mellitus type 2 (T2D) is scarce, although the incidence of both disorders is increasing.

Methods: This "retro-pro" study compared 65 T2D patients to a control group of 130 age- and sex-matched non-diabetics. GERD was confirmed by gastroscopy, manometry, pH-metry and barium swallow.

Results: In patients with T2D compared to controls, dysphagia (32.3% vs. 13.1%; p = 0.001) and globus sensation (27.7% vs. 13.8%; p = 0.021) were found more frequently, whereas heartburn (76.9% vs. 88.5%; p = 0.046) and regurgitation (47.7% vs. 72.3%; p= 0.001) were predominant in non-diabetics. Despite higher body mass indices (31.1 ± 5.2 vs. 27.7 ± 3.7 kg/m²; p < 0.001), hiatal hernia was less frequent in T2D patients compared to controls (60.0% vs. 90.8%, p < 0.001). Lower oesophageal sphincter (LES) pressure was higher in patients with T2D (median 10.0 vs. 7.2 mmHg, p = 0.016). DeMeester scores did not differ between the groups. Helicobacter pylori infections were more common in T2D patients (26.2% vs. 7.7%, p = 0.001). Barrett metaplasia (21.5% vs. 17.7%), as well as low- (10.8% vs. 3.8%) and high-grade dysplasia (1.5% vs. 0%) were predominant in T2D patients.

Conclusions: T2D patients exhibit different GERD symptoms, higher LES pressures and a decreased prevalence of hiatal hernia than non-diabetics, which may be related to worse oesophageal motility and, thus, a more functional rather than anatomical cause of GERD. Low-grade dysplasia was more than twice as high in T2D than in non-diabetics patients.

Trial Registration: Ethics committee of the Medical University of Vienna, IRB number 720/2011.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1471-230X-13-132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3765380PMC
August 2013