Publications by authors named "Ihor Huk"

44 Publications

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

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

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

Effects of metformin on adipose-derived stromal cell (ADSC) - Breast cancer cell lines interaction.

Life Sci 2020 Nov 31;261:118371. Epub 2020 Aug 31.

Department of Plastic and Reconstructive Surgery, Medical University of Vienna, Vienna, Austria.

Aims: Metformin is a clinical drug administered to patients to treat type 2 diabetes mellitus that was found to be associated with a lower risk of occurrence of cancer and cancer-related death. The present study investigated the effects of metformin on human adipose-derived stromal cells (ADSC) - breast cancer cell line interactions.

Main Methods: ADSCs grown from lipoaspirates were tested for growth-stimulating and migration-controlling activity on breast cancer cell lines after pretreatment with metformin. Furthermore, secreted proteins of ADSCs, phosphorylation of intracellular proteins and the effect of metformin on adipocytic differentiation of ADSCs were assayed.

Key Findings: Compared to breast cancer cell lines (4.0 ± 3.5% reduction of proliferation), 2 mM metformin significantly inhibited the proliferation of ADSC lines (19.2 ± 8.4% reduction of proliferation). This effect on ADSCs seems to be mediated by altered phosphorylation of GSK-3, CREB and PRAS40. Furthermore, treatment with metformin abolished the induction of differentiation of three ADSC lines to adipocytes. 1 and 2 mM metformin significantly impaired the migration of breast cancer cell lines MDA-MB-231 and MDA-MB-436 in scratch assays.

Significance: Metformin showed low direct inhibitory effects on breast cancer cell lines at physiological concentrations but exerted a significant retardation of the growth and the adipocytic differentiation of ADSCs. Thus, the anticancer activity of metformin in breast cancer at physiological drug concentrations seems to be mediated by an indirect mechanism that lowers the supportive activity of ADSCs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.lfs.2020.118371DOI Listing
November 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

Insight into the expression of toll-like receptors 2 and 4 in patients with abdominal aortic aneurysm.

Mol Biol Rep 2020 Apr 7;47(4):2685-2692. Epub 2020 Mar 7.

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

An abdominal aortic aneurysm (AAA) is a relatively common, life-threatening disease prevalent in persons over the age of 65. In recent years, an increasing number of studies have suggested that pattern-recognition receptors (PRRs), including Toll-like receptors (TLRs), may serve as important regulators in the development of AAAs. In this study, we evaluated the TLR2 and TLR4 expression in the aortic wall and blood of patients with AAA. The TLR2 and TLR4 mRNA expression were significantly higher in the blood of patients with AAA than in the blood of healthy volunteers (p = 0.009 and p = 0.010, respectively). The expression of TLR2 and TLR4 transcripts was also higher in the blood compared with the aortic wall tissue of AAA patients (p = 0.001 for both). Higher TLR2 protein expression was observed in the aortic wall of AAA patients compared with the blood (p = 0.026). A significantly higher concentration of TNF-α and IL-4 in patients with AAA than in healthy volunteers (p < 0.001 for both) was noticed. This study suggests that TLR2 may play a role in the inflammatory response in the aorta, both locally and systemically, in patients with AAA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11033-020-05366-xDOI Listing
April 2020

Biliverdin reductase deficiency triggers an endothelial-to-mesenchymal transition in human endothelial cells.

Arch Biochem Biophys 2019 12 5;678:108182. Epub 2019 Nov 5.

Department of Medical Biotechnology, Faculty of Biochemistry Biophysics and Biotechnology, Jagiellonian University, 30-387, Krakow, Poland; Department of Surgery, Division of Vascular Surgery, Medical University of Vienna, 1090, Vienna, Austria. Electronic address:

Endothelial dysfunction accompanied by the loss of endothelial cell phenotype plays an essential role in cardiovascular diseases. Here, we report that knockdown of biliverdin reductase (BVR), the enzyme of the heme degradation pathway converting biliverdin to bilirubin, shifts endothelial phenotype of the primary human aortic endothelial cells (HAECs) to mesenchymal-like one. It is reflected by the loss of endothelial markers and angiogenic response, with concomitant acquiring of mesenchymal markers, increased migratory capacity and metalloproteinase activity. BVR-deficiency induces the activity of Nrf2 transcription factor and increases heme oxygenase-1 (HO-1) level, which is accompanied by the reduction of cellular heme content, increase in a free iron fraction and oxidative stress. Accordingly, the phenotype of BVR-deficient cells can be mimicked by hemin or iron overload. Depletion of HO-1 in BVR-deficient ECs abrogates the increase in intracellular free iron and oxidative stress, preventing the loss of endothelial markers. Treatment of BVR-deficient cells with bilirubin does not rescue the endothelial phenotype of HAECs. Unlike BLVRA mRNA level, the expression of HMOX1, HMOX1:BLVRA ratio and HO-1 protein level positively correlate with abdominal aortic aneurysm size in clinical samples. Collectively, the non-enzymatic activity of BVR contributes to the maintenance of healthy endothelial phenotype through the prevention of HO-1-dependent iron-overload, oxidative stress and subsequent endothelial-to-mesenchymal transition (EndMT).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.abb.2019.108182DOI Listing
December 2019

Interaction of Adipose-Derived Stromal Cells with Breast Cancer Cell Lines.

Plast Reconstr Surg 2019 08;144(2):207e-217e

From the Divisions of Plastic and Reconstructive Surgery and Vascular Surgery, Department of Surgery, and the Department of Oral and Maxillofacial Surgery, Medical University of Vienna.

Background: Assisted lipotransfer for breast reconstruction involves the isolation and supplementation of adipose-derived stromal cells. This procedure has raised concerns regarding safety with respect to promotion of tumor growth and relapse. Several in vitro and animal experimental studies have indicated increased survival, growth, and invasive characteristics of breast cancer cells on interaction with adipose-derived stromal cells. These results seem to be in poor concordance with clinical observations of a low rate of cancer recurrences after assisted lipotransfer.

Methods: The authors investigated the effects of adipose-derived stromal cells and adipose-derived stromal cells differentiated into adipocytes and fibroblasts on five breast cancer cell lines (i.e., T47D, MCF-7, BT20, MDA-MB-231, and ZR-75-1) and MCF-10A, a nonmalignant counterpart.

Results: Conditioned media of adipose-derived stromal cells stimulated the proliferation of breast cancer cell lines depending on the individual adipose-derived stromal cell-breast cancer cell line combination. Conditioned media of adipose-derived stromal cells differentiated into adipocytes gave a lower response, and conditioned media of fibroblasts were also active. A putative cancer stem cell-like phenotype was not increased by adipose-derived stromal cell-conditioned media, no physical interaction of cancer cells with adipose-derived stromal cells was detectable on scanning electron microscopy, and cell migration was not enhanced. Adipogenic differentiation of adipose-derived stromal cells indicated that hepatocyte growth factor, insulin-like growth factor-binding protein-3, insulin-like growth factor-binding protein-6, interleukin-6, CCL2/MCP-1, and macrophage colony-stimulating factor are not linked to the proliferative activity of conditioned media.

Conclusion: The results indicate that the adipose-derived stromal cells used for assisted lipotransfer are not expected to increase the risk of tumor recurrence to a major degree in correspondence with the clinical observation of the affected breast cancer patients.

Clinical Question/level Of Evidence: Therapeutic, V.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/PRS.0000000000005839DOI Listing
August 2019

Differential expression of Plg-R and its effects on migration of proinflammatory monocyte and macrophage subsets.

Blood 2019 08 20;134(6):561-567. Epub 2019 Jun 20.

Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria.

Membrane-bound plasmin is used by immune cells to degrade extracellular matrices, which facilitates migration. The plasminogen receptor Plg-R is expressed by immune cells, including monocytes and macrophages. Among monocytes and macrophages, distinct subsets can be distinguished based on cell surface markers and pathophysiological function. We investigated expression of Plg-R by monocyte and macrophage subsets and whether potential differential expression might have functional consequences for cell migration. Proinflammatory CD14CD16 human monocytes and Ly6C mouse monocytes expressed the highest levels of Plg-R and bound significantly more plasminogen compared with the other respective subsets. Proinflammatory human macrophages, generated by polarization with lipopolysaccharide and interferon-γ, showed significantly higher expression of Plg-R compared with alternatively activated macrophages, polarized with interleukin-4 and interleukin-13. Directional migration of proinflammatory monocytes was plasmin dependent and was abolished by anti-Plg-R monoclonal antibody, ε-amino-caproic acid, aprotinin, and the aminoterminal fragment of urokinase-type plasminogen activator. In an in vivo peritonitis model, significantly less Ly6C monocyte recruitment was observed in Plg-R compared with Plg-R mice. Immunohistochemical analysis of human carotid plaques and adipose tissue showed that proinflammatory macrophages also exhibited high levels of Plg-R in vivo. Our data demonstrate higher expression of Plg-R on proinflammatory monocyte and macrophage subsets that impacts their migratory capacity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/blood.2018850420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6688429PMC
August 2019

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

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

Expression of Proteolytic Enzymes by Small Cell Lung Cancer Circulating Tumor Cell Lines.

Cancers (Basel) 2019 Jan 19;11(1). Epub 2019 Jan 19.

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

Small cell lung cancer (SCLC) is an aggressive type of lung cancer which disseminates vigorously and has a dismal prognosis. Metastasis of SCLC is linked to an extremely high number of circulating tumor cells (CTCs), which form chemoresistant spheroids, termed tumorospheres. Intravasation and extravasation during tumor spread requires the activity of a number of proteases to disintegrate the stroma and vascular tissue. Generation of several permanent SCLC CTC lines allowed us to screen for the expression of 35 proteases using Western blot arrays. Cell culture supernatants of two CTC lines, namely BHGc7 and 10, were analyzed for secreted proteases, including matrix metalloproteinases (MMPs), ADAM/TS, cathepsins, kallikreins, and others, and compared to proteases expressed by SCLC cell lines (GLC14, GLC16, NCI-H526 and SCLC26A). In contrast to NCI-H526 and SCLC26A, MMP-9 was highly expressed in the two CTC lines and in GLC16 derived of a relapse. Furthermore, cathepsins (S, V, X/Z/P, A and D) were highly expressed in the CTC lines, whereas ADAM/TS and kallikreins were not detectable. In conclusion, SCLC CTCs express MMP-9 and a range of cathepsins for proteolysis and, aside from tissue degradation, these enzymes are involved in cell signaling, survival, and the chemoresistance of tumor cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers11010114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6357007PMC
January 2019

Simvastatin Treatment Upregulates HO-1 in Patients with Abdominal Aortic Aneurysm but Independently of Nrf2.

Oxid Med Cell Longev 2018 20;2018:2028936. Epub 2018 Mar 20.

Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.

Heme oxygenase-1 (HO-1), encoded by gene and regulated by Nrf2 transcription factor, is a cytoprotective enzyme. Its deficiency may exacerbate abdominal aortic aneurysm (AAA) development, which is also often associated with hyperlipidemia. Beneficial effects of statins, the broadly used antilipidemic drugs, were attributed to modulation of Nrf2/HO-1 axis. However, the effect of statins on Nrf2/HO-1 pathway in patients with AAA has not been studied yet. We analyzed AAA tissue from patients treated with simvastatin ( = 28) or without statins ( = 14). Simvastatin treatment increased HO-1 protein level in AAA, both in endothelial cells (ECs) and in smooth muscle cells (SMCs), but increased Nrf2 localization was restricted only to vasa vasorum. Nrf2 target genes , , and expression remained unchanged in AAA. studies showed that simvastatin raises HO-1 protein level slightly in ECs and to much higher extent in SMCs, which is not related to Nrf2/ARE activation, although expression is upregulated by simvastatin in both cell types. In conclusion, simvastatin-induced modulation of HO-1 level in ECs and SMCs is not related to Nrf2/ARE activity. Likewise, divergent HO-1 and Nrf2 localization together with stable expression of Nrf2 target genes, including , in AAA tissue denotes Nrf2 independency.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2018/2028936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5883937PMC
October 2018

Analysis of host Toll-like receptor 3 and RIG-I-like receptor gene expression in patients with abdominal aortic aneurysm.

J Vasc Surg 2018 12 19;68(6S):39S-46S. Epub 2018 Mar 19.

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

Objective: Abdominal aortic aneurysm (AAA) is a vascular disease relatively common in the elderly population. Although some events that contribute to the development and progression of AAA are known, there are limited data examining the association of Toll-like receptor 3 (TLR3) and RIG-I-like receptor expression with the pathogenesis of AAAs. In this study, we investigated the gene and protein expression of TLR3 and RIG-I-like receptors (RIG-I and MDA5) in aortic wall and blood of AAA patients and examined the relationship between their expression and immune response.

Methods: Total RNA was extracted from aortic wall tissues and blood samples collected from 20 patients with AAA and blood samples of 17 healthy volunteers without aortic aneurysm. To evaluate the DDX58 (RIG-I), IFIH1 (MDA5), and TLR3 gene expression level, quantitative real-time polymerase chain reaction was used. Extracellular cytokine and pattern recognition receptor levels were quantified by enzyme-linked immunosorbent assays.

Results: TLR3, RIG-I, and MDA5 were constitutively expressed in both aortic tissues and blood samples from AAA patients and healthy volunteers. In patients with AAA, higher TLR3 expression in aortic tissues than in blood was found (P = .004). The DDX58 messenger RNA expression was higher in blood of patients with AAA compared with healthy subjects (P = .021). A significantly higher level of plasma interleukin 4 was noticed in patients with AAA than in healthy individuals (P = .008).

Conclusions: This study suggests that RIG-I and TLR3 seem to be important factors in the pathogenesis of AAA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jvs.2017.10.087DOI Listing
December 2018

Lower levels of Caveolin-1 and higher levels of endothelial nitric oxide synthase are observed in abdominal aortic aneurysm patients treated with simvastatin.

Acta Biochim Pol 2018 15;65(1):111-118. Epub 2018 Mar 15.

Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland.

This study was undertaken to verify whether simvastatin modulates Cav-1/eNOS expression, and if this modulation is associated with changes in pro- and anti-inflammatory cytokine and Toll-like receptor 4 (TLR4) level in abdominal aortic aneurysm (AAA). It is a 1:2 case-control study of non-statin (n=12) and simvastatin-treated patients (n=24) who underwent open AAA repair. Simvastatin treatment decreased Cav-1 (p<0.05) and increased eNOS expression (p<0.01) in the AAA wall. These changes might be dose dependent. The changes in Cav-1 and eNOS were associated with a trend towards decreased IL-6 and IL-17 concentration (p>0.05) and increased IL-10 concentration (p=0.055); however, TLR4 expression was unaffected, suggesting that simvastatin influences Cav-1 and eNOS in the AAA wall by other mechanisms. Simvastatin may modulate Cav-1 and eNOS expression in the aneurysmal wall, indicating a potentially beneficial role for statins in AAA patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18388/abp.2017_2305DOI Listing
October 2018

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

IL-33 stimulates the release of procoagulant microvesicles from human monocytes and differentially increases tissue factor in human monocyte subsets.

Thromb Haemost 2017 06 11;117(7):1379-1390. Epub 2017 May 11.

Johann Wojta, Department of Internal Medicine II and Core Facilities, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria, Telephone: +43 1 40400/73500, Fax: +43 1 40400/73587, E-mail: or, Agneta Siegbahn, Department of Medical Sciences, Clinical Chemistry and Science for Life Laboratory, University Hospital and Uppsala University, SE 751 85 Uppsala, Sweden, Tel.: +46 18 611 4251, Fax: +46 18 552562, E-mail:

Monocytes and monocyte-derived microvesicles (MVs) are the main source of circulating tissue factor (TF). Increased monocyte TF expression and increased circulating levels of procoagulant MVs contribute to the formation of a prothrombotic state in patients with cardiovascular disease. Interleukin (IL)-33 is a pro-inflammatory cytokine involved in atherosclerosis and other inflammatory diseases, but its role in regulating thrombosis is still unclear. The aim of the present study was to investigate the effects of IL-33 on the procoagulant properties of human monocytes and monocyte-derived MVs. IL-33 induced a time- and concentration-dependent increase of monocyte TF mRNA and protein levels via binding to the ST2-receptor and activation of the NF-κB-pathway. The IL-33 treated monocytes also released CD14+TF+ MVs and IL-33 was found to increase the TF activity of both the isolated monocytes and monocyte-derived MVs. The monocytes were classified into subsets according to their CD14 and CD16 expression. Intermediate monocytes (IM) showed the highest ST2 receptor expression, followed by non-classical monocytes (NCM), and classical monocytes (CM). IL-33 induced a significant increase of TF only in the IM (p<0.01), with a tendency in NCM (p=0.06), but no increase was observed in CM. Finally, plasma levels of IL-33 were positively correlated with CD14+TF+ MVs in patients undergoing carotid endarterectomy (r=0.480; p=0.032; n=20). We hereby provide novel evidence that the proinflammatory cytokine IL-33 induces differential TF expression and activity in monocyte subsets, as well as the release of procoagulant MVs. In this manner, IL-33 may contribute to the formation of a prothrombotic state characteristic for cardiovascular disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1160/TH16-10-0784DOI Listing
June 2017

Successful Treatment of a Ruptured Extracranial Vertebral Artery Aneurysm with Onyx Instillation.

Ann Vasc Surg 2016 Oct 6;36:290.e7-290.e10. Epub 2016 Jul 6.

Department of Cardiovascular and Interventional Radiology, Medical University of Vienna, Vienna, Austria.

The rupture of an extracranial vertebral artery aneurysm has only been rarely described in the literature and treatment options are therefore not standardized. Here we report the successful endovascular repair of a spontaneously ruptured extracranial left vertebral artery aneurysm using Onyx instillation. A 48-year-old woman was transferred to our clinic after having been intubated due to a massive hematoma of the left neck. A contrast-enhanced computed tomography (CT) showed a rupture of the left extracranial vertebral artery. Several issues complicated the therapeutic decision making in this rare case: first, the patient showed multiple aneurysms in CT angiography; therefore a connective tissue disease could not be excluded. Furthermore, as anamnestic work-up revealed that several episodes of postoperative bleeding and open surgery at this anatomic location are rarely performed, risks for postoperative complications were high. Therefore, the patient was hemodynamically stabilized and the ruptured aneurysm was treated in an endovascular approach with Onyx instillation and coil embolization. Complete exclusion of the aneurysm was achieved without periprocedural or neurological complications. Successful repair was confirmed by CT angiography on the first postoperative day as well as 12 months after the intervention. In conclusion, this case shows that endovascular Onyx embolization of ruptured vertebral aneurysms is a save and feasible method.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.avsg.2016.02.036DOI Listing
October 2016

Interleukin-33 stimulates GM-CSF and M-CSF production by human endothelial cells.

Thromb Haemost 2016 08 12;116(2):317-27. Epub 2016 May 12.

Svitlana Demyanets, MD, PhD, Department of Laboratory Medicine, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria, Tel.: +43 1 40400 73516, Fax: +43 1 40400 73587, E-mail:

Interleukin (IL)-33, a member of the IL-1 family of cytokines, is involved in various inflammatory conditions targeting amongst other cells the endothelium. Besides regulating the maturation and functions of myeloid cells, granulocyte macrophage-colony stimulating factor (GM-CSF) and macrophage-CSF (M-CSF) have been shown to play a role in such pathologies too. It was the aim of our study to investigate a possible influence of IL-33 on GM-CSF and M-CSF production by human endothelial cells. IL-33, but not IL-18 or IL-37, stimulated GM-CSF and M-CSF mRNA expression and protein production by human umbilical vein endothelial cells (HUVECs) and human coronary artery ECs (HCAECs) through the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway in an IL-1-independent way. This effect was inhibited by the soluble form of ST2 (sST2), which is known to act as a decoy receptor for IL-33. The 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor fluvastatin could also be shown to moderately reduce the IL-33-mediated effect on M-CSF, but not on GM-CSF expression. In addition, IL-33, IL-1β, GM-CSF and M-CSF were detected in endothelial cells of human carotid atherosclerotic plaques using immunofluorescence. Upregulation of GM-CSF and M-CSF production by human endothelial cells, an effect that appears to be mediated by NF-κB and to be independent of IL-1, may be an additional mechanism through which IL-33 contributes to inflammatory activation of the vessel wall.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1160/TH15-12-0917DOI Listing
August 2016

Tissue factor is induced by interleukin-33 in human endothelial cells: a new link between coagulation and inflammation.

Sci Rep 2016 05 4;6:25171. Epub 2016 May 4.

Department of Internal Medicine II, Medical University of Vienna, Austria.

Tissue factor (TF) is the primary trigger of coagulation. Elevated levels of TF are found in atherosclerotic plaques, and TF leads to thrombus formation when released upon plaque rupture. Interleukin (IL)-33 was previously shown to induce angiogenesis and inflammatory activation of endothelial cells (ECs). Here, we investigated the impact of IL-33 on TF in human ECs, as a possible new link between inflammation and coagulation. IL-33 induced TF mRNA and protein in human umbilical vein ECs and coronary artery ECs. IL-33-induced TF expression was ST2- and NF-κB-dependent, but IL-1-independent. IL-33 also increased cell surface TF activity in ECs and TF activity in ECs-derived microparticles. IL-33-treated ECs reduced coagulation time of whole blood and plasma but not of factor VII-deficient plasma. In human carotid atherosclerotic plaques (n = 57), TF mRNA positively correlated with IL-33 mRNA expression (r = 0.691, p < 0.001). In this tissue, IL-33 and TF protein was detected in ECs and smooth muscle cells by immunofluorescence. Furthermore, IL-33 and TF protein co-localized at the site of clot formation within microvessels in plaques of patients with symptomatic carotid stenosis. Through induction of TF in ECs, IL-33 could enhance their thrombotic capacity and thereby might impact on thrombus formation in the setting of atherosclerosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/srep25171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4855148PMC
May 2016

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

T cell-activated signaling pathways and locally produced cytokines as potential targets in celiac disease.

Curr Drug Targets 2015 ;16(3):226-32

Department of Biochemistry, Medical University of Lodz, Mazowiecka 6/8 St., 92-215 Lodz, Poland.

Celiac disease (CD) is an autoimmune disease induced by an autoimmune reaction to indigested gluten, which occurs in genetically predisposed population. The etiology of CD is linked to innate and adaptive immunity, mostly mediated by lymphocytes, especially T cells, infiltrating into the small intestinal wall. The subpopulations of T cells that infiltrate inflamed intestinal tissues comprise various CD4+ T cells and CD8+ T cells. The plethora of T cell subtypes activated in CD leads to simultaneous activation of different signaling cascades including GATA1, NF-kB, JAK or STAT5 the activity of which may be modified by diet or drugs. It was recently showed that food allergens may accelerate CD by altering the interaction between IL-15 and CD4+ T cells in the activation of CD8+ T cells. Increased levels of cytokines like IL-15 are considered to play a role in CD development. Furthermore it was showed that some drugs like tofacitinib or ruxolitinib may influence CD by blocking IL-15 signaling and CD8+ T cell activity. This mini-review will summarize the current knowledge on the role of CD4+ T cell and CD8+ T cell in clinical and experimental CD and will describe how T cell-activated signaling pathways and locally released proteins may be influenced by dietary factors and drugs used in CD treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1389450116666150304104627DOI Listing
January 2016

Interleukin-33 induces expression of adhesion molecules and inflammatory activation in human endothelial cells and in human atherosclerotic plaques.

Arterioscler Thromb Vasc Biol 2011 Sep 7;31(9):2080-9. Epub 2011 Jul 7.

Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria.

Objective: Interleukin (IL)-33 is the most recently described member of the IL-1 family of cytokines and it is a ligand of the ST2 receptor. While the effects of IL-33 on the immune system have been extensively studied, the properties of this cytokine in the cardiovascular system are much less investigated. Methods/Results- We show here that IL-33 promoted the adhesion of human leukocytes to monolayers of human endothelial cells and robustly increased vascular cell adhesion molecule-1, intercellular adhesion molecule-1, endothelial selectin, and monocyte chemoattractant protein-1 protein production and mRNA expression in human coronary artery and human umbilical vein endothelial cells in vitro as well as in human explanted atherosclerotic plaques ex vivo. ST2-fusion protein, but not IL-1 receptor antagonist, abolished these effects. IL-33 induced translocation of nuclear factor-κB p50 and p65 subunits to the nucleus in human coronary artery endothelial cells and human umbilical vein endothelial cells and overexpression of dominant negative form of IκB kinase 2 or IκBα in human umbilical vein endothelial cells abolished IL-33-induced adhesion molecules and monocyte chemoattractant protein-1 mRNA expression. We detected IL-33 and ST2 on both protein and mRNA level in human carotid atherosclerotic plaques.

Conclusions: We hypothesize that IL-33 may contribute to early events in endothelial activation characteristic for the development of atherosclerotic lesions in the vessel wall, by promoting adhesion molecules and proinflammatory cytokine expression in the endothelium.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/ATVBAHA.111.231431DOI Listing
September 2011

Improved survival after abdominal aortic aneurysm rupture by offering both open and endovascular repair.

Arch Surg 2008 Jun;143(6):544-9; discussion 550

Department of Vascular Surgery, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.

Background: In the treatment of ruptured abdominal aortic aneurysm (rAAA), the results of open graft replacement (OGR) have remained constant but discouraging for the last 4 decades. Provided suitable anatomy, elective endovascular abdominal aortic aneurysm repair (EVAR) is less invasive and leads to improved perioperative mortality. Thus, it is reasonable to assume that endovascular treatment should improve the results of rAAA therapy.

Objective: To determine whether the use of both endovascular and open repair of rAAA leads to improved results.

Design: A single-center, retrospective analysis of 89 patients suffering from rAAA treated either by EVAR or OGR.

Patients: From October 1999 until July 2006, a consecutive series of patients with rAAA were analyzed. Time was divided into 2 periods of 41 months. During the first period, 42 patients were treated by OGR exclusively. Period 2 started with the availability of an EVAR protocol to treat rAAA; 31 patients received open repair while 16 patients underwent EVAR.

Main Outcome Measures: Kaplan-Meier survival estimates were calculated and compared.

Results: Survival estimates showed a statistically significant reduction in overall postoperative mortality following the introduction of EVAR (P < .03). The 90-day overall mortality rate was reduced from 54.8% to 27.7% during the second period (P < .01). Survival of patients older than 75.5 years was especially improved (75% vs 28.6%; P < .01). There was a parallel pattern of significant reduction of the mortality rate after OGR to 29% (P < .03).

Conclusion: Offering both EVAR and OGR to patients with rAAA leads to significant improvements in postoperative survival.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/archsurg.143.6.544DOI Listing
June 2008

Repair of abdominal aortic aneurysms: the benefits of offering both endovascular and open surgical techniques.

Perspect Vasc Surg Endovasc Ther 2006 Sep;18(3):238-46

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

Two treatment options are available for abdominal aortic aneurysms (AAAs): open surgical technique with graft replacement and endovascular aortic aneurysm repair (EVAR) as a minimally invasive procedure. The intention of this review is to highlight the advantages of both procedures and to demonstrate that offering both procedures is beneficial for the patient when he or she makes the important decision regarding which treatment to select. A comparative evaluation of both treatment options is offered as well as a short description of the risk of rupture and its consequences. The authors discuss the latest literature as well as their own experiences. An innovative statistical approach-the propensity score-based Cox model-is presented to evaluate the 2 treatment options. The benefits of offering both EVAR and open surgery permit optimal management of AAA for the individual patient and tailor the treatment to his or her organ dysfunctions and impaired physical status. In addition, EVAR offers a treatment option for otherwise incurable high-risk patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1531003506296861DOI Listing
September 2006

Combined enzymatic and antioxidative treatment reduces ischemia-reperfusion injury in rabbit skeletal muscle.

J Surg Res 2006 Jun 3;133(2):150-8. Epub 2006 Feb 3.

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

Background: Ischemia/reperfusion (I/R) injury is characterized by the production of oxygen-free radicals leading to disturbances in vasomotility (microvascular constriction) and microvascular permeability (interstitial edema formation). The objective was to evaluate the effect of the combined antioxidative and enzymatic preparation Phlogenzym on I/R injury of skeletal muscle.

Materials And Methods: A rabbit hindlimb model of I/R (2.5/2 h) was used (IR group). Phlogenzym, containing rutin, trypsin, and bromelain, was applied enterally (60 mg/kg body weight) as a bolus 30 min prior to ischemia (Ph group). Sham-operated animals served as controls (CO group). Plasma malondialdehyde, potassium, and microvascular perfusion (monitored by laser flowmetry) were assessed. Histomorphometry and electron microscopy were performed from major adductor muscles.

Results: Two hours after reperfusion, potassium levels were significantly elevated in IR compared to Ph group (6.7 +/- 1.2 versus 4.9 +/- 0.9 mmol/l, P < 0.006). Enhanced lipid peroxidation, apparent by increased plasma malondialdehyde levels, was ameliorated in the Ph group (1.0 +/- 0.1 versus 0.7 +/- 0.1 nmol/ml, P < 0.0001). No-reflow (reduction of blood flow by 62% in IR group) was not observed in the Ph group (P < 0.004). Phlogenzym treatment prevented microvascular constriction (17.6 +/- 2.3 versus 12.6 +/- 1.1 microm(2), P < 0.0001) and mollified interstitial edema (21.5 +/- 2.0 versus 26.0 +/- 3.7%, P < 0.017), resulting in mild ultrastructural alterations in contrast to pronounced sarcolemmal and mitochondrial damage in untreated rabbits.

Conclusions: Phlogenzym had a protective effect on skeletal muscle during I/R injury expressed by prevention of no-reflow and preservation of muscle tissue.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jss.2005.12.005DOI Listing
June 2006

Abdominal aortic aneurysms and concomitant diseases requiring surgical intervention: simultaneous operation vs staged treatment using endoluminal stent grafting.

Arch Surg 2005 Jul;140(7):686-91

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

Hypothesis: To investigate whether staged or synchronous treatment of infrarenal abdominal aortic aneurysms (AAAs) and concomitant diseases (CDs) requiring surgical repair plays a clinical role. We considered endovascular aneurysm repair (EVAR) in particular.

Design: Review of a prospectively gathered database.

Setting: Tertiary care university teaching hospital.

Patients: We reviewed a total of 946 patients receiving elective AAA exclusion from 1980 through 2002. We divided the period into 2 observation intervals: 1980-1994, when only open graft replacement was available (n = 331), and 1995-2002, with 615 patients (326 who had open graft replacement and 289 who had EVAR). With regard to the physical status, expressed by the score from the American Society of Anesthesiologists (Park Ridge, Ill), we recorded in-hospital mortality rates and checked possible differences.

Main Outcome Measures: Indications for therapy and mortality rates before and after the availability of EVAR.

Results: During the first interval, 14 simultaneous operations were carried out. During the second period, 19 patients received simultaneous operations while 49 underwent staged treatment using EVAR. The overall mortality rate was 3.7%. Irrespective of the American Society of Anesthesiologists classification, the mortality rate for patients who had EVAR was 0% in comparison with 13.6% for patients in American Society of Anesthesiologists class 3 or 4 after open graft replacement (P<.03).

Conclusions: The coincidence of a patient having both an AAA and a CD is rare but should not be neglected. Staged treatment of AAAs using EVAR followed by surgical therapy for CDs can be an effective causal therapy with an acceptable mortality rate provided that suitable aneurysm anatomy exists.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/archsurg.140.7.686DOI Listing
July 2005

Endografting increases total volume of AAA repairs but not at the expense of open surgery: experience in more than 1000 patients.

J Endovasc Ther 2005 Jun;12(3):274-9

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

Purpose: To compare the volume of open graft replacements (OGR) for abdominal aortic aneurysm (AAA) versus endovascular aneurysm repairs (EVAR) over time and after modifying selection criteria.

Methods: A review was conducted of 1021 consecutive patients who underwent AAA repair from 1989 through 2002: 496 elective OGRs for infrarenal AAAs (STANDARD), 289 elective EVARs for infrarenal AAAs, 59 complex OGRs for suprarenal AAAs, and 177 emergent OGRs for ruptured AAAs. Patients from 1995 to 2002 were divided into 2 groups based on shifting treatment strategies; 454 patients were treated by STANDARD or EVAR at the surgeon's discretion between 1995 and 2000 (post EVAR). The second group comprised 161 patients treated in 2001-2002 after the introduction of "high-risk" screening criteria (age > or = 72 years, diabetes mellitus, renal dysfunction, impaired pulmonary function, or ASA class IV) that dictated EVAR whenever anatomically feasible. For comparison, 170 STANDARD repairs performed in the 6 years prior to EVAR served as a control.

Results: While surgery for ruptured AAAs remained fairly stable over the 14-year period, the number of patients undergoing elective repair increased due to the implementation of EVAR. During the 6 years after its introduction, EVAR averaged 34.3 patients per year; after 2001, the annual frequency of EVAR increased to 41.5 (p > 0.05). In like fashion, the rate of STANDARD repairs increased to 41.3 patients per year versus 28.3 before EVAR (p = 0.032). ASA class IV patients increased by almost 9 fold in the recent period versus pre EVAR (p = 0.006). The overall mortality after elective infrarenal AAA repair decreased between the pre and post EVAR periods (6.5% versus 3.7%, p > 0.05) and fell still further to 1.2% in the most recent period (p = 0.021 versus pre EVAR).

Conclusions: The implementation of an EVAR program increases the total volume of AAA repairs but does not reduce open surgical procedures. By allocating patients to EVAR or open repair based their risk factors, mortality was markedly reduced.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1583/04-1397MR.1DOI Listing
June 2005