Publications by authors named "Michael Neuhaus"

17 Publications

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Ethnic comparison in takotsubo syndrome: novel insights from the International Takotsubo Registry.

Clin Res Cardiol 2021 May 19. Epub 2021 May 19.

Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.

Background: Ethnic disparities have been reported in cardiovascular disease. However, ethnic disparities in takotsubo syndrome (TTS) remain elusive. This study assessed differences in clinical characteristics between Japanese and European TTS patients and determined the impact of ethnicity on in-hospital outcomes.

Methods: TTS patients in Japan were enrolled from 10 hospitals and TTS patients in Europe were enrolled from 32 hospitals participating in the International Takotsubo Registry. Clinical characteristics and in-hospital outcomes were compared between Japanese and European patients.

Results: A total of 503 Japanese and 1670 European patients were included. Japanese patients were older (72.6 ± 11.4 years vs. 68.0 ± 12.0 years; p < 0.001) and more likely to be male (18.5 vs. 8.4%; p < 0.001) than European TTS patients. Physical triggering factors were more common (45.5 vs. 32.0%; p < 0.001), and emotional triggers less common (17.5 vs. 31.5%; p < 0.001), in Japanese patients than in European patients. Japanese patients were more likely to experience cardiogenic shock during the acute phase (15.5 vs. 9.0%; p < 0.001) and had a higher in-hospital mortality (8.2 vs. 3.2%; p < 0.001). However, ethnicity itself did not appear to have an impact on in-hospital mortality. Machine learning approach revealed that the presence of physical stressors was the most important prognostic factor in both Japanese and European TTS patients.

Conclusion: Differences in clinical characteristics and in-hospital outcomes between Japanese and European TTS patients exist. Ethnicity does not impact the outcome in TTS patients. The worse in-hospital outcome in Japanese patients, is mainly driven by the higher prevalence of physical triggers.

Trial Registration: URL: https://www.clinicaltrials.gov ; Unique Identifier: NCT01947621.
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http://dx.doi.org/10.1007/s00392-021-01857-4DOI Listing
May 2021

How is neck dissection performed in Oral and Maxillofacial Surgery? Results of a representative nationwide survey among university and non-university hospitals in Germany.

Clin Oral Investig 2021 May 29;25(5):3007-3019. Epub 2021 Mar 29.

Department of Oral and Maxillofacial Surgery, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.

Introduction: Neck dissection (ND) is a surgical procedure addressing cervical lymph nodes and metastases in patients with oral squamous cell carcinoma (OSCC). The aim of this study was to analyze clinical decisions regarding indications and variations of ND in Oral and Maxillofacial Surgery (OMFS) in Germany.

Material And Methods: A nationwide survey of the German Association of Oral and Maxillofacial Surgery was performed using dynamic online questionnaires including 38 questions. Data about oncological centers, case numbers, and staging procedures were collected. Relevant aspects, such as inclusion of level IIb and levels IV and V to ND, uni- vs. bilateral ND, and the influence of extra-nodal extension (ENE) of metastases on extension of ND were evaluated.

Results: Eighty-four OMFS of university and non-university hospitals participated in the study (responding rate 21.4%). Sixty-six (78.57%) stated to work at certified cancer centers and 53.57% of the hospitals treated between 50 and 100 OSCC cases per year. CT and/or MRI of the head and neck was performed in most of the staging procedures. Level IIb was included by 71 (93.42%) of the participants in selective ND. Levels IV and V were included by 53 (69.74%) in node-positive neck. In solitary ipsilateral metastases (ENE-), 49 participants (62.82%) stated to perform exclusively an ipsilateral ND and 40 (51.95%) stated to perform only an ipsilateral ND in ENE+.

Conclusion: This study demonstrated a high rate of certified cancer centers in Germany showing differences regarding staging procedures, indications, and extension of ND, especially in increasingly complex cases.

Clinical Relevance: Clinical decisions regarding ND are dependent on case-individual aspects and must be decided individually.
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http://dx.doi.org/10.1007/s00784-020-03622-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113132PMC
May 2021

Prognostic impact of acute pulmonary triggers in patients with takotsubo syndrome: new insights from the International Takotsubo Registry.

ESC Heart Fail 2021 06 13;8(3):1924-1932. Epub 2021 Mar 13.

Department of Cardiology, Charité, Campus Rudolf Virchow, Berlin, Germany.

Aims: Acute pulmonary disorders are known physical triggers of takotsubo syndrome (TTS). This study aimed to investigate prevalence of acute pulmonary triggers in patients with TTS and their impact on outcomes.

Methods And Results: Patients with TTS were enrolled from the International Takotsubo Registry and screened for triggering factors and comorbidities. Patients were categorized into three groups (acute pulmonary trigger, chronic lung disease, and no lung disease) to compare clinical characteristics and outcomes. Of the 1670 included patients with TTS, 123 (7%) were identified with an acute pulmonary trigger, and 194 (12%) had a known history of chronic lung disease. The incidence of cardiogenic shock was highest in patients with an acute pulmonary trigger compared with those with chronic lung disease or without lung disease (17% vs. 10% vs. 9%, P = 0.017). In-hospital mortality was also higher in patients with an acute pulmonary trigger than in the other two groups, although not significantly (5.7% vs. 1.5% vs. 4.2%, P = 0.13). Survival analysis demonstrated that patients with an acute pulmonary trigger had the worst long-term outcome (P = 0.002). The presence of an acute pulmonary trigger was independently associated with worse long-term mortality (hazard ratio 2.12, 95% confidence interval 1.33-3.38; P = 0.002).

Conclusions: The present study demonstrates that TTS is related to acute pulmonary triggers in 7% of all TTS patients, which accounts for 21% of patients with physical triggers. The presence of acute pulmonary trigger is associated with a severe in-hospital course and a worse long-term outcome.
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http://dx.doi.org/10.1002/ehf2.13165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120351PMC
June 2021

Self-centering second-generation patient-specific functionalized implants for deep orbital reconstruction.

J Stomatol Oral Maxillofac Surg 2020 Dec 30. Epub 2020 Dec 30.

Department of Oral and Maxillofacial Surgery, Hannover Medical School, Hannover, Germany. Electronic address:

Deep and complete reconstruction of the orbital cavity has been shown to be essential for preventing enophthalmos and hypoglobus in patients with orbital defects or deformities. Additively manufactured patient-specific titanium implants provide unlimited options in design. However, implant malpositioning can still occur, even when intraoperative imaging and navigation are used. In this study, we investigated novel orbital implants containing features facilitating self-centering. Accuracy of implant placement and reconstruction of the orbital dimensions were compared retrospectively between self-centering second-generation patient-specific functionalized orbital implants (study group) and CAD-based individualized implants (control group). Design features of implants in the study group included functionalization with navigation tracks, a preventive design, and flanges - so called stabilizers - towards opposite orbital walls. Implant position was evaluated by fusion of preoperative virtual plans and the post-therapeutic imaging. Aberrances were quantified by 3D heatmap analysis. 31 patients were assigned to the study group and 50 to the control group, respectively. In the study group, most implants were designed with either one (n = 18, 58.06%) or two (n = 10, 32.26%) stabilizers. Twice (6.45%), one stabilizer had to be shortened intraoperatively. Implant fit analysis revealed a significantly more precise (p < 0.001) positioning in the study group (n = 22/31) than in the control group (n = 42/50). Self-centering second-generation patient-specific functionalized orbital implants showed significantly more accurate implant positioning, facilitating the transformation of virtual plans into patient's anatomy. The presented design provides an additional instrument for intraoperative quality control besides intraoperative imaging and navigation.
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http://dx.doi.org/10.1016/j.jormas.2020.12.007DOI Listing
December 2020

Coexistence and outcome of coronary artery disease in Takotsubo syndrome.

Eur Heart J 2020 09;41(34):3255-3268

Department of Cardiology, Kantonsspital Lucerne, Lucerne, Switzerland.

Aims: Takotsubo syndrome (TTS) is an acute heart failure syndrome, which shares many features with acute coronary syndrome (ACS). Although TTS was initially described with angiographically normal coronary arteries, smaller studies recently indicated a potential coexistence of coronary artery disease (CAD) in TTS patients. This study aimed to determine the coexistence, features, and prognostic role of CAD in a large cohort of patients with TTS.

Methods And Results: Coronary anatomy and CAD were studied in patients diagnosed with TTS. Inclusion criteria were compliance with the International Takotsubo Diagnostic Criteria for TTS, and availability of original coronary angiographies with ventriculography performed during the acute phase. Exclusion criteria were missing views, poor quality of angiography loops, and angiography without ventriculography. A total of 1016 TTS patients were studied. Of those, 23.0% had obstructive CAD, 41.2% had non-obstructive CAD, and 35.7% had angiographically normal coronary arteries. A total of 47 patients (4.6%) underwent percutaneous coronary intervention, and 3 patients had acute and 8 had chronic coronary artery occlusion concomitant with TTS, respectively. The presence of CAD was associated with increased incidence of shock, ventilation, and death from any cause. After adjusting for confounders, the presence of obstructive CAD was associated with mortality at 30 days. Takotsubo syndrome patients with obstructive CAD were at comparable risk for shock and death and nearly at twice the risk for ventilation compared to an age- and sex-matched ACS cohort.

Conclusions: Coronary artery disease frequently coexists in TTS patients, presents with the whole spectrum of coronary pathology including acute coronary occlusion, and is associated with adverse outcome.

Trial Registration: ClinicalTrials.gov number: NCT01947621.
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http://dx.doi.org/10.1093/eurheartj/ehaa210DOI Listing
September 2020

Age-Related Variations in Takotsubo Syndrome.

J Am Coll Cardiol 2020 04;75(16):1869-1877

Krankenhaus "Maria Hilf" Medizinische Klinik, Stadtlohn, Germany.

Background: Takotsubo syndrome (TTS) occurs predominantly in post-menopausal women but is also found in younger patients.

Objectives: This study aimed to investigate age-related differences in TTS.

Methods: Patients diagnosed with TTS and enrolled in the International Takotsubo Registry between January 2011 and February 2017 were included in this analysis and were stratified by age (younger: ≤50 years, middle-age: 51 to 74 years, elderly: ≥75 years). Baseline characteristics, hospital course, as well as short- and long-term mortality were compared among groups.

Results: Of 2,098 TTS patients, 242 (11.5%) patients were ≤50 years of age, 1,194 (56.9%) were 51 to 74 years of age, and 662 (31.6%) were ≥75 years of age. Younger patients were more often men (12.4% vs. 10.9% vs. 6.3%; p = 0.002) and had an increased prevalence of acute neurological (16.3% vs. 8.4% vs. 8.8%; p = 0.001) or psychiatric disorders (14.1% vs. 10.3% vs. 5.6%; p < 0.001) compared with middle-aged and elderly TTS patients. Furthermore, younger patients had more often cardiogenic shock (15.3% vs. 9.1% vs. 8.1%; p = 0.004) and had a numerically higher in-hospital mortality (6.6% vs. 3.6% vs. 5.1%; p = 0.07). At multivariable analysis, younger (odds ratio: 1.60; 95% confidence interval: 0.86 to 3.01; p = 0.14) and older age (odds ratio: 1.09; 95% confidence interval: 0.66 to 1.80; p = 0.75) were not independently associated with in-hospital mortality using the middle-aged group as a reference. There were no differences in 60-day mortality rates among groups.

Conclusions: A substantial proportion of TTS patients are younger than 50 years of age. TTS is associated with severe complications requiring intensive care, particularly in younger patients.
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http://dx.doi.org/10.1016/j.jacc.2020.02.057DOI Listing
April 2020

Impact of aspirin on takotsubo syndrome: a propensity score-based analysis of the InterTAK Registry.

Eur J Heart Fail 2020 02 20;22(2):330-337. Epub 2019 Dec 20.

Department of Internal Medicine III, Heart Center University of Cologne, Cologne, Germany.

Aims: The aim of the present study was to investigate the impact of aspirin on prognosis in takotsubo syndrome (TTS).

Methods And Results: Patients from the International Takotsubo (InterTAK) Registry were categorized into two groups based on aspirin prescription at discharge. A comparison of clinical outcomes between groups was performed using an adjusted analysis with propensity score (PS) stratification; results from the unadjusted analysis were also reported to note the effect of the PS adjustment. Major adverse cardiac and cerebrovascular events (MACCE: a composite of death, myocardial infarction, TTS recurrence, stroke or transient ischaemic attack) were assessed at 30-day and 5-year follow-up. A total of 1533 TTS patients with known status regarding aspirin prescription at discharge were included. According to the adjusted analysis based on PS stratification, aspirin was not associated with a lower hazard of MACCE at 30-day [hazard ratio (HR) 1.24, 95% confidence interval (CI) 0.50-3.04, P = 0.64] or 5-year follow-up (HR 1.11, 95% CI 0.78-1.58, P = 0.58). These results were confirmed by sensitivity analyses performed with alternative PS-based methods, i.e. covariate adjustment and inverse probability of treatment weighting.

Conclusion: In the present study, no association was found between aspirin use in TTS patients and a reduced risk of MACCE at 30-day and 5-year follow-up. These findings should be confirmed in adequately powered randomized controlled trials. ClinicalTrials.gov Identifier: NCT01947621.
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http://dx.doi.org/10.1002/ejhf.1698DOI Listing
February 2020

Intraventricular Thrombus Formation and Embolism in Takotsubo Syndrome: Insights From the International Takotsubo Registry.

Arterioscler Thromb Vasc Biol 2020 01 26;40(1):279-287. Epub 2019 Nov 26.

Service de cardiologie, Hôpitaux Universitaires de Genève, Switzerland (P. Meyer, J.D.A.).

Objective: Takotsubo syndrome (TTS) is characterized by acute left ventricular dysfunction, which can contribute to intraventricular thrombus and embolism. Still, prevalence and clinical impact of thrombus formation and embolic events on outcome of TTS patients remain unclear. This study aimed to investigate clinical features and outcomes of patients with and without intraventricular thrombus or embolism. Additionally, factors associated with thrombus formation or embolism, as well as predictors for mortality, were identified. Approach and Results: TTS patients enrolled in the International Takotsubo Registry at 28 centers in Australia, Europe, and the United States were dichotomized according to the occurrence/absence of intraventricular thrombus or embolism. Patients with intraventricular thrombus or embolism were defined as the ThrombEmb group. Of 1676 TTS patients, 56 (3.3%) patients developed intraventricular thrombus and/or embolism following TTS diagnosis (median time interval, 2.0 days [range, 0-38 days]). Patients in the ThrombEmb group had a different clinical profile including lower left ventricular ejection fraction, higher prevalence of the apical type, elevated levels of troponin and inflammatory markers, and higher prevalence of vascular disease. In a Firth bias-reduced penalized-likelihood logistic regression model apical type, left ventricular ejection fraction ≤30%, previous vascular disease, and a white blood cell count on admission >10×10 cells/μL emerged as independent predictors for thrombus formation or embolism.

Conclusions: Intraventricular thrombus or embolism occur in 3.3% of patients in the acute phase of TTS. A simple risk score including clinical parameters associated with intraventricular thrombus formation or embolism identifies patients at increased risk.

Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01947621.
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http://dx.doi.org/10.1161/ATVBAHA.119.313491DOI Listing
January 2020

Accuracy of virtual surgical planning of orthognathic surgery with aid of CAD/CAM fabricated surgical splint-A novel 3D analyzing algorithm.

J Craniomaxillofac Surg 2017 Dec 29;45(12):1962-1970. Epub 2017 Jul 29.

Department of Craniomaxillofacial Surgery, Hannover Medical School, Germany. Electronic address:

The benefit of computer-assisted planning in orthognathic surgery has been extensively documented over the last decade. This study aims to evaluate the accuracy of a virtual orthognathic surgical plan by a novel three dimensional (3D) analysis method. Ten patients who required orthognathic surgery were included in this study. A virtual surgical plan was achieved by the combination of a 3D skull model acquired from computed tomography (CT) and surface scanning of the upper and lower dental arch respectively and final occlusal position. Osteotomies and movement of maxilla and mandible were simulated by Dolphin Imaging 11.8 Premium (Dolphin Imaging and Management Solutions, Chatsworth, CA). The surgical plan was transferred to surgical splints fabricated by means of Computer Aided Design/Computer Aided Manufacturing (CAD/CAM). Differences of three dimensional measurements between the virtual surgical plan and postoperative results were evaluated. The results from all parameters showed that the virtual surgical plans were successfully transferred by the assistance of CAD/CAM fabricated surgical splint. Wilcoxon's signed rank test showed that no statistically significant deviation between surgical plan and post-operational result could be detected. However, deviation of angle U1 axis-HP and distance of A-CP could not fulfill the clinical success criteria. Virtual surgical planning and CAD/CAM fabricated surgical splint are proven to facilitate treatment planning and offer an accurate surgical result in orthognathic surgery.
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http://dx.doi.org/10.1016/j.jcms.2017.07.016DOI Listing
December 2017

Methionine restriction slows down senescence in human diploid fibroblasts.

Aging Cell 2014 Dec 1;13(6):1038-48. Epub 2014 Oct 1.

Institute for Biomedical Aging Research (IBA), Universität Innsbruck, Rennweg 10, 6020, Innsbruck, Austria.

Methionine restriction (MetR) extends lifespan in animal models including rodents. Using human diploid fibroblasts (HDF), we report here that MetR significantly extends their replicative lifespan, thereby postponing cellular senescence. MetR significantly decreased activity of mitochondrial complex IV and diminished the accumulation of reactive oxygen species. Lifespan extension was accompanied by a significant decrease in the levels of subunits of mitochondrial complex IV, but also complex I, which was due to a decreased translation rate of several mtDNA-encoded subunits. Together, these findings indicate that MetR slows down aging in human cells by modulating mitochondrial protein synthesis and respiratory chain assembly.
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http://dx.doi.org/10.1111/acel.12266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4326930PMC
December 2014

Safety and tolerability of intensified, N-terminal pro brain natriuretic peptide-guided compared with standard medical therapy in elderly patients with congestive heart failure: results from TIME-CHF.

Eur J Heart Fail 2013 Aug 10;15(8):910-8. Epub 2013 May 10.

Maastricht University Medical Center, CARIM, Maastricht, The Netherlands.

Aims: NT-proBNP-guided therapy results in intensification of medical heart failure (HF) therapy and is suggested to improve outcome. However, it is feared that an intensified, NT-proBNP-guided therapy carries a risk of adverse effects. Therefore, the safety and tolerability of NT-proBNP-guided therapy in the Trial of Intensified vs standard Medical therapy in Elderly patients with Congestive Heart Failure (TIME-CHF) was assessed.

Methods And Results: A total of 495 chronic HF patients, aged ≥60, with an LVEF ≤45%, NYHA class ≥II, randomized to NT-proBNP-guided or symptom-guided therapy and ≥1 month follow-up were included in the present safety analysis. All adverse events (AEs) were recorded during the 18-month trial period. A total of 5212 AEs were noted, 433 of them serious. NT-proBNP-guided therapy led to a higher up-titration of HF medication and was well tolerated, with a dropout rate (12% vs. 11%, P = 1.0) and AE profile [number of AEs/patient-year 4.7 (2.8-9.4) vs. 5.4 (2.7-11.4), P = 0.69; number of severe AEs/patient-year 0.7 (0-2.7) vs. 1.3 (0-3.9), P = 0.21] similar to that of symptom-guided therapy, although most subjects in both treatment groups (96% vs. 95%, P = 0.55) experienced at least one AE. Age and number of co-morbidities were associated with AEs and interacted with the safety profile of NT-proBNP-guided therapy: positive effects were more frequent in younger and less co-morbid patients whereas potential negative effects-although small and related to non-severe AEs only-were only seen in the older and more co-morbid patients.

Conclusions: NT-proBNP-guided therapy is safe in elderly and highly co-morbid HF patients. Trial registration ISRCTN43596477.
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http://dx.doi.org/10.1093/eurjhf/hft079DOI Listing
August 2013

Identification of microRNA-mRNA functional interactions in UVB-induced senescence of human diploid fibroblasts.

BMC Genomics 2013 Apr 4;14:224. Epub 2013 Apr 4.

Institute for Biomedical Aging Research, Austrian Academy of Sciences, Rennweg 10, Innsbruck 6020, Austria.

Background: Cellular senescence can be induced by a variety of extrinsic stimuli, and sustained exposure to sunlight is a key factor in photoaging of the skin. Accordingly, irradiation of skin fibroblasts by UVB light triggers cellular senescence, which is thought to contribute to extrinsic skin aging, although molecular mechanisms are incompletely understood. Here, we addressed molecular mechanisms underlying UVB induced senescence of human diploid fibroblasts.

Results: We observed a parallel activation of the p53/p21(WAF1) and p16(INK4a)/pRb pathways. Using genome-wide transcriptome analysis, we identified a transcriptional signature of UVB-induced senescence that was conserved in three independent strains of human diploid fibroblasts (HDF) from skin. In parallel, a comprehensive screen for microRNAs regulated during UVB-induced senescence was performed which identified five microRNAs that are significantly regulated during the process. Bioinformatic analysis of miRNA-mRNA networks was performed to identify new functional mRNA targets with high confidence for miR-15a, miR-20a, miR-20b, miR-93, and miR-101. Already known targets of these miRNAs were identified in each case, validating the approach. Several new targets were identified for all of these miRNAs, with the potential to provide new insight in the process of UVB-induced senescence at a genome-wide level. Subsequent analysis was focused on miR-101 and its putative target gene Ezh2. We confirmed that Ezh2 is regulated by miR-101 in human fibroblasts, and found that both overexpression of miR-101 and downregulation of Ezh2 independently induce senescence in the absence of UVB irradiation. However, the downregulation of miR-101 was not sufficient to block the phenotype of UVB-induced senescence, suggesting that other UVB-induced processes induce the senescence response in a pathway redundant with upregulation of miR-101.

Conclusion: We performed a comprehensive screen for UVB-regulated microRNAs in human diploid fibroblasts, and identified a network of miRNA-mRNA interactions mediating UVB-induced senescence. In addition, miR-101 and Ezh2 were identified as key players in UVB-induced senescence of HDF.
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http://dx.doi.org/10.1186/1471-2164-14-224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4008267PMC
April 2013

Cystathionine beta synthase modulates senescence of human endothelial cells.

Aging (Albany NY) 2012 Oct;4(10):664-73

Institute for Biomedical Aging Research (IBA), University of Innsbruck, Innsbruck, Austria.

Availability of methionine is known to modulate the rate of aging in model organisms, best illustrated by the observation that dietary methionine restriction extends the lifespan of rodents. However, the underlying mechanisms are incompletely understood. In eukaryotic cells, methionine can be converted to cysteine through the reverse transsulfuration pathway thereby modulating intracellular methionine availability. Whereas previous results obtained in yeast and fruit flies suggest that alterations in the reverse transsulfuration pathway modulate the rate of aging, it is not known whether this function is conserved in evolution. Here we show that depletion of cystathionine beta synthase (CBS), a rate limiting enzyme in the reverse transsulfuration pathway, induces premature senescence in human endothelial cells. We found that CBS depletion induces mild mitochondrial dysfunction and increases the sensitivity of endothelial cells to homocysteine, a known inducer of endothelial cell senescence and an established risk factor for vascular disease. Our finding that CBS deficiency induces endothelial cell senescencein vitro, involving both mitochondrial dysfunction and increased susceptibility of the cells to homocysteine, suggests a new mechanism linking CBS deficiency to vascular aging and disease.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3517937PMC
http://dx.doi.org/10.18632/aging.100491DOI Listing
October 2012

Role of endonuclease G in senescence-associated cell death of human endothelial cells.

Exp Gerontol 2010 Aug 6;45(7-8):638-44. Epub 2010 Mar 6.

Institute for Biomedical Aging Research, Austrian Academy of Sciences, Rennweg 10, Innsbruck, Austria.

Mitotic cells in culture show a limited replicative potential and after extended subculturing undergo a terminal growth arrest termed cellular senescence. When cells reach the senescent phenotype, this is accompanied by a significant change in the cellular phenotype and massive changes in gene expression, including the upregulation of secreted factors. In human fibroblasts, senescent cells also acquire resistance to apoptosis. In contrary, in human endothelial cells, both replicative and stress-induced premature senescence is accompanied by increased cell death; however mechanisms of cell death are poorly explored. In this communication, we addressed the role of endonuclease G (EndoG), a mitochondrial mediator of caspase-independent cell death, in senescence-associated cell death of human endothelial cells. Using immunofluorescence microscopy, we found, that EndoG is localized in the mitochondria in young cells, but relocalizes to the nucleus upon senescence. When EndoG gene expression was downregulated by lentiviral shRNA vectors, we found a significant reduction in the replicative life span and a corresponding increase in cell death. We also observed a slight shift in the cell death phenotype from necrosis to apoptosis. Together these observations suggest an important role of EndoG in the senescence program of human endothelial cells.
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http://dx.doi.org/10.1016/j.exger.2010.03.002DOI Listing
August 2010

MRI of intimal sarcoma of the pulmonary arteries.

Circ Cardiovasc Imaging 2009 Sep;2(5):e37-9

Clinic for Cardiology, University Hospital Zurich, Switzerland.

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http://dx.doi.org/10.1161/CIRCIMAGING.108.840793DOI Listing
September 2009
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