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| 2. |
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| 3. |
- Coustenis, A., et al.
(författare)
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TandEM : Titan and Enceladus mission
- 2009
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Ingår i: Experimental astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 23:3, s. 893-946
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Tidskriftsartikel (refereegranskat)abstract
- TandEM was proposed as an L-class (large) mission in response to ESA's Cosmic Vision 2015-2025 Call, and accepted for further studies, with the goal of exploring Titan and Enceladus. The mission concept is to perform in situ investigations of two worlds tied together by location and properties, whose remarkable natures have been partly revealed by the ongoing Cassini-Huygens mission. These bodies still hold mysteries requiring a complete exploration using a variety of vehicles and instruments. TandEM is an ambitious mission because its targets are two of the most exciting and challenging bodies in the Solar System. It is designed to build on but exceed the scientific and technological accomplishments of the Cassini-Huygens mission, exploring Titan and Enceladus in ways that are not currently possible (full close-up and in situ coverage over long periods of time). In the current mission architecture, TandEM proposes to deliver two medium-sized spacecraft to the Saturnian system. One spacecraft would be an orbiter with a large host of instruments which would perform several Enceladus flybys and deliver penetrators to its surface before going into a dedicated orbit around Titan alone, while the other spacecraft would carry the Titan in situ investigation components, i.e. a hot-air balloon (MontgolfiSre) and possibly several landing probes to be delivered through the atmosphere.
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| 4. |
- Zhang, W, et al.
(författare)
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INKILN is a novel long noncoding RNA promoting vascular smooth muscle inflammation via scaffolding MKL1 and USP10
- 2023
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Ingår i: bioRxiv : the preprint server for biology. - : Cold Spring Harbor Laboratory.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundActivation of vascular smooth muscle cells (VSMCs) inflammation is vital to initiate vascular disease. However, the role of human-specific long noncoding RNAs (lncRNAs) in VSMC inflammation is poorly understood.MethodsBulk RNA-seq in differentiated human VSMCs revealed a novel human-specific lncRNA calledINflammatory MKL1InteractingLongNoncoding RNA (INKILN).INKILNexpression was assessed in multiple in vitro and ex vivo models of VSMC phenotypic modulation and human atherosclerosis and abdominal aortic aneurysm (AAA) samples. The transcriptional regulation ofINKILNwas determined through luciferase reporter system and chromatin immunoprecipitation assay. Both loss- and gain-of-function approaches and multiple RNA-protein and protein-protein interaction assays were utilized to uncover the role ofINKILNin VSMC proinflammatory gene program and underlying mechanisms. Bacterial Artificial Chromosome (BAC) transgenic (Tg) mice were utilized to studyINKLINexpression and function in ligation injury-induced neointimal formation.ResultsINKILNexpression is downregulated in contractile VSMCs and induced by human atherosclerosis and abdominal aortic aneurysm.INKILNis transcriptionally activated by the p65 pathway, partially through a predicted NF-κB site within its proximal promoter.INKILNactivates the proinflammatory gene expression in cultured human VSMCs and ex vivo cultured vessels. Mechanistically,INKILNphysically interacts with and stabilizes MKL1, a key activator of VSMC inflammation through the p65/NF-κB pathway.INKILNdepletion blocks ILIβ-induced nuclear localization of both p65 and MKL1. Knockdown ofINKILNabolishes the physical interaction between p65 and MKL1, and the luciferase activity of an NF-κB reporter. Further,INKILNknockdown enhances MKL1 ubiquitination, likely through the reduced physical interaction with the deubiquitinating enzyme, USP10.INKILNis induced in injured carotid arteries and exacerbates ligation injury-induced neointimal formation in BAC Tg mice.ConclusionsThese findings elucidate an important pathway of VSMC inflammation involving anINKILN/MKL1/USP10 regulatory axis. Human BAC Tg mice offer a novel and physiologically relevant approach for investigating human-specific lncRNAs under vascular disease conditions.
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| 6. |
- Batra, Gorav, et al.
(författare)
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Biomarker-Based Prediction of Recurrent Ischemic Events in Patients With Acute Coronary Syndromes
- 2022
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Ingår i: Journal of the American College of Cardiology. - : Elsevier. - 0735-1097 .- 1558-3597. ; 80:18, s. 1735-1747
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In patients with acute coronary syndrome (ACS), there is residual and variable risk of recurrent ischemic events.OBJECTIVES: This study aimed to develop biomarker-based prediction models for 1-year risk of cardiovascular (CV) death and myocardial infarction (MI) in patients with ACS undergoing percutaneous coronary intervention.METHODS: We included 10,713 patients from the PLATO (A Comparison of Ticagrelor [AZD6140] and Clopidogrel in Patients With Acute Coronary Syndrome) trial in the development cohort and externally validated in 3,508 patients from the TRACER (Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome) trial. Variables contributing to risk of CV death/MI were assessed using Cox regression models, and a score was derived using subsets of variables approximating the full model.RESULTS: There were 632 and 190 episodes of CV death/MI in the development and validation cohorts. The most important predictors of CV death/MI were the biomarkers, growth differentiation factor 15, and N-terminal pro-B-type natriuretic peptide, which had greater prognostic value than all candidate variables. The final model included 8 items: age (A), biomarkers (B) (growth differentiation factor 15 and N-terminal pro-B-type natriuretic peptide), and clinical variables (C) (extent of coronary artery disease, previous vascular disease, Killip class, ACS type, P2Y12 inhibitor). The model, named ABC-ACS ischemia, was well calibrated and showed good discriminatory ability for 1-year risk of CV death/MI with C-indices of 0.71 and 0.72 in the development and validation cohorts, respectively. For CV death, the score performed better, with C-indices of 0.80 and 0.84 in the development and validation cohorts, respectively.CONCLUSIONS: An 8-item score for the prediction of CV death/MI was developed and validated for patients with ACS undergoing percutaneous coronary intervention. The ABC-ACS ischemia score showed good calibration and discrimination and might be useful for risk prediction and decision support in patients with ACS. (A Comparison of Ticagrelor [AZD6140] and Clopidogrel in Patients With Acute Coronary Syndrome [PLATO]; NCT00391872; Trial to Assess the Effects of Vorapaxar [SCH 530348; MK-5348] in Preventing Heart Attack and Stroke in Participants With Acute Coronary Syndrome [TRACER]; NCT00527943)
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| 7. |
- Clark, M. S., et al.
(författare)
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Multi-omics for studying and understanding polar life
- 2023
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Ingår i: Nature Communications. - : NATURE PORTFOLIO. - 2041-1723. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Polar ecosystems are experiencing amongst the most rapid rates of regional warming on Earth. Here, we discuss ‘omics’ approaches to investigate polar biodiversity, including the current state of the art, future perspectives and recommendations. We propose a community road map to generate and more fully exploit multi-omics data from polar organisms. These data are needed for the comprehensive evaluation of polar biodiversity and to reveal how life evolved and adapted to permanently cold environments with extreme seasonality. We argue that concerted action is required to mitigate the impact of warming on polar ecosystems via conservation efforts, to sustainably manage these unique habitats and their ecosystem services, and for the sustainable bioprospecting of novel genes and compounds for societal gain.
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| 8. |
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| 9. |
- Hettrich, Sebastian, et al.
(författare)
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Atmospheric drag, occultation 'N' ionospheric scintillation (ADONIS) mission proposal: Alpbach Summer School 2013 team orange
- 2015
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Ingår i: Journal of Space Weather and Space Climate. - : EDP Sciences. - 2115-7251. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- The Atmospheric Drag, Occultation ‘N’ Ionospheric Scintillation mission (ADONIS) studies the dynamics of the terrestrial thermosphere and ionosphere in dependency of solar events over a full solar cycle in Low Earth Orbit (LEO). The objectives are to investigate satellite drag with in-situ measurements and the ionospheric electron density profiles with radio occultation and scintillation measurements. A constellation of two satellites provides the possibility to gain near real-time data (NRT) about ionospheric conditions over the Arctic region where current coverage is insufficient. The mission shall also provide global high-resolution data to improve assimilative ionospheric models. The low-cost constellation can be launched using a single Vega rocket and most of the instruments are already space-proven allowing for rapid development and good reliability. From July 16 to 25, 2013, the Alpbach Summer School 2013 was organised by the Austrian Research Promotion Agency (FFG), the European Space Agency (ESA), the International Space Science Institute (ISSI) and the association of Austrian space industries Austrospace in Alpbach, Austria. During the workshop, four teams of 15 students each independently developed four different space mission proposals on the topic of "Space Weather: Science, Missions and Systems", supported by a team of tutors. The present work is based on the mission proposal that resulted from one of these teams’ efforts.
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| 10. |
- Jones, G. H., et al.
(författare)
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The dust halo of Saturn's largest icy moon, Rhea
- 2008
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 319:5868, s. 1380-1384
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Tidskriftsartikel (refereegranskat)abstract
- Saturn's moon Rhea had been considered massive enough to retain a thin, externally generated atmosphere capable of locally affecting Saturn's magnetosphere. The Cassini spacecraft's in situ observations reveal that energetic electrons are depleted in the moon's vicinity. The absence of a substantial exosphere implies that Rhea's magnetospheric interaction region, rather than being exclusively induced by sputtered gas and its products, likely contains solid material that can absorb magnetospheric particles. Combined observations from several instruments suggest that this material is in the form of grains and boulders up to several decimetres in size and orbits Rhea as an equatorial debris disk. Within this disk may reside denser, discrete rings or arcs of material.
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| 11. |
- Kempf, W., et al.
(författare)
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MUM1 expression in cutaneous CD30+ lymphoproliferative disorders : A valuable tool for the distinction between lymphomatoid papulosis and primary cutaneous anaplastic large-cell lymphoma
- 2008
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Ingår i: British Journal of Dermatology. - : Oxford University Press (OUP). - 0007-0963 .- 1365-2133. ; 158:6, s. 1280-1287
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Tidskriftsartikel (refereegranskat)abstract
- Background: Primary cutaneous CD30+ lymphoproliferative disorders include lymphomatoid papulosis (LyP) and primary cutaneous CD30+ anaplastic large T-cell lymphoma (ALCL). Because of overlapping histological features, it is impossible to distinguish ALCL from LyP on histological grounds. MUM1 (Multiple Myeloma oncogene 1) is expressed in systemic ALCL and classical Hodgkin lymphoma. MUM1 expression has not been studied in detail in CD30+ lymphoproliferative disorders. Objectives: To examine the expression of MUM1 in CD30+ lymphoproliferative disorders and to assess its value as a diagnostic marker. Methods: Thirty-one formalin-fixed paraffin-embedded specimens of LyP (n = 15), primary cutaneous ALCL (n = 10), secondary cutaneous infiltrates of systemic ALCL (n = 4) and secondary cutaneous Hodgkin lymphoma (n = 2) were analysed by immunohistochemistry with a monoclonal antibody against MUM1. Results Results: Positive staining for MUM1 was observed in 13 cases of LyP (87%), two cases of primary cutaneous ALCL (20%), four cases of secondary cutaneous ALCL (100%) and two cases of secondary cutaneous Hodgkin lymphoma (100%). In 11 of 13 LyP cases (85%), MUM1 was displayed by the majority, i.e. 50-90%, of the tumour cells. In contrast to LyP and secondary cutaneous ALCL, only two cases of primary cutaneous ALCL (20%) harboured MUM1-positive tumour cells. There was a statistically significant difference in the expression of MUM1 between LyP and primary cutaneous ALCL (P = 0.002) and between primary cutaneous ALCL and secondary cutaneous ALCL (P = 0.015). Conclusions: MUM1 expression is a valuable tool for the distinction of LyP and ALCL and thus represents a novel adjunctive diagnostic marker in CD30+ lymphoproliferative disorders. © 2008 The Authors.
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| 12. |
- Kutzner, H., et al.
(författare)
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CD123-positive plasmacytoid dendritic cells in primary cutaneous marginal zone b-cell lymphoma : Diagnostic and pathogenetic implications
- 2009
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Ingår i: American Journal of Surgical Pathology. - 0147-5185 .- 1532-0979. ; 33:9, s. 1307-1313
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Tidskriftsartikel (refereegranskat)abstract
- The histogenesis of primary cutaneous marginal zone B-cell lymphoma (PCMZL) has not yet been clarified. Plasmacytoid dendritic cells (PDC) play a crucial role in the initiation of immune responses and activation of T-cells and B-cells. We analyzed the presence of PDC by immunohistochemistry in various forms of primary cutaneous B-cell lymphomas and in B-cell pseudolymphomas. Clusters of CD123 PDC were observed in all PCMZL (23 of 23 cases; 100%) and in two-thirds of cutaneous B-cell pseudolymphomas (14 of 22; 64%), but only in a minority of primary cutaneous follicle center lymphoma (4 of 31; 13%) and not in primary cutaneous diffuse large B-cell lymphoma, leg type. CD123+ PDC clusters were found in close proximity to monoclonal plasma cells and T-cells and were already present at high numbers in early lesions and initial recurrences of PCMZL. In conclusion, the detection of larger clusters of PDC in PCMZL provides a useful adjunctive diagnostic marker and suggests a pathogenetically relevant role of these cells in PCMZL. Furthermore, the occurrence of PDC could explain the high number of T-cells typically found in PCMZL. We propose considering PCMZL as a unique and potentially antigen-driven neoplasm with PDC, T-cells, and B-cells as the constitutive tumor components. Copyright © 2009 by Lippincott Williams & Wilkins.
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| 14. |
- Meyer, H., et al.
(författare)
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Test of the law of gravitation at small accelerations
- 2012
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Ingår i: General Relativity and Gravitation. - : Springer Science and Business Media LLC. - 0001-7701 .- 1572-9532. ; 44:10, s. 2537-2545
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Tidskriftsartikel (refereegranskat)abstract
- Newton's Law of Gravitation has been tested at small values a of the acceleration, down to a a parts per thousand 10(-10) ms(-2), the approximate value of MOND's constant a (0). Within experimental errors no deviations from Newton's Law were found. A comparison with six versions of the MOND interpolation function is given. Under the assumptions made in this paper one of the versions can be excluded.
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| 15. |
- Mitteldorf, C., et al.
(författare)
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Expression of programmed death-1 (CD279) in primary cutaneous B-cell lymphomas with correlation to lymphoma entities and biological behaviour
- 2013
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Ingår i: British Journal of Dermatology. - : Blackwell Publishing Ltd. - 0007-0963 .- 1365-2133. ; 169:6, s. 1212-1218
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Tidskriftsartikel (refereegranskat)abstract
- Background Programmed death-1 (PD-1/CD279) is a cell-surface protein expressed in activated T cells and a subset of T lymphocytes including follicular helper T cells (TFH). The interaction between PD-1 and its ligands plays a role in immune response and evasion of malignancies. In nodal follicular lymphoma, the number of intratumoral PD-1-positive lymphocytes is associated with overall survival. Objectives To investigate 28 cases of primary cutaneous B-cell lymphoma, including the subtypes PCFCL (n = 10), PCMZL (n = 10) and DLBCL-LT (n = 8) for the number and density of PD-1-positive cells. Methods Immunohistochemical staining and a computerized morphometric analysis for evaluation were applied. The results were correlated with the clinical outcome. To distinguish between activated T cells and TFH we performed PD-1/bcl-6 double staining and compared these results with CXCL-13 staining. Double staining for PD-1 and PAX-5 was used to investigate whether tumour cells were positive for PD-1. Results The PD-1-positive cells represented tumour-infiltrating T cells (TILs). Only a minor subset was represented by TFH. Patients with DLBCL-LT had a significantly lower number of PD-1-positive TILs than those with PCMZL (P = 0·012) and PCFCL (P = 0·002) or both (P = 0·001). The difference between PCMZL and PCFCL did not reach significance (P = 0·074). The tumour cells were negative for PD-1. Conclusions A higher number of PD-1-expressing cells was found in indolent PCMZL and PCFCL than in high-malignant DLBCL-LT. The PD-1-positive cells represented not only TFH, but also other activated T cells as a part of the tumour microenvironment. The tumour cells in all investigated types of PCBCL did not show aberrant PD-1 expression. What’s already known about this topic? In nodal follicular lymphoma, the number of intratumoral programmed death (PD)-1-positive lymphocytes is associated with overall survival. No data exist for primary cutaneous B-cell lymphoma (PCBCL). What does this study add? A higher number of PD-1-expressing cells was found in indolent primary cutaneous marginal zone lymphoma and primary cutaneous follicle centre lymphoma, in contrast to the more aggressive diffuse large B-cell lymphoma, leg type. PD-1-positive cells do not represent only follicular helper T cells. The tumour cells in all investigated types of PCBCL did not show aberrant PD-1 expression. © 2013 British Association of Dermatologists.
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| 16. |
- Mitteldorf, C., et al.
(författare)
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Galectin-3 Expression in Primary Cutaneous CD30-Positive Lymphoproliferative Disorders and Transformed Mycosis Fungoides
- 2015
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Ingår i: Dermatology. - : S. Karger AG. - 1018-8665 .- 1421-9832. ; 231:2, s. 164-170
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Tidskriftsartikel (refereegranskat)abstract
- Background: In nodal anaplastic large cell lymphoma, strong expression of galectin-3 (Gal-3) has been found, but only very few cases of primary cutaneous lymphoma have so far been examined. Objectives: To investigate 11 primary cutaneous anaplastic large cell lymphomas (PCALCL), 47 lymphomatoid papuloses (LYP) and 14 cases of transformed mycosis fungoides with CD30 expression (MF-T) for Gal-3 expression. Methods: A Gal-3 score was applied using a photo-based morphometric evaluation program. Double staining for CD30 and Gal-3 was performed. Furthermore, we recorded the cellular and extracellular sublocalization of the signal. Results: The Gal-3 expression in CD30+ tumor cells was significantly lower in MF-T in contrast to CD30+ lymphoproliferative disorders (CD30 LPD; p < 0.001), but we found no differences between PCALCL and LYP (p = 0.42). In PCALCL Gal-3 was more often localized in the cytoplasm in contrast to LYP, in which an equal distribution in the cytoplasm and the nucleus was more common (p = 0.9). Conclusions: The lower Gal-3 expression in MF-T in comparison to CD30 LPD might be an additional criterion to differentiate both entities. The different sublocalization of the Gal-3 signal might reflect a different biological function and behavior. © 2015 S. Karger AG, Basel.
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| 17. |
- Mitteldorf, C., et al.
(författare)
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PD-1 and PD-L1 in neoplastic cells and the tumor microenvironment of Merkel cell carcinoma
- 2017
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Ingår i: Journal of cutaneous pathology. - : Blackwell Publishing Ltd. - 0303-6987 .- 1600-0560. ; 44:9, s. 740-746
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Tidskriftsartikel (refereegranskat)abstract
- Background: Merkel cell carcinoma (MCC) is an aggressive neoplasm, which is often associated with Merkel cell polyomavirus (MCPyV). Programmed death-1 (PD-1) and its ligand PD-L1 are key players of the tumor microenvironment (TME). Methods: Fourteen paraffin-embedded tissue samples of MCC were stratified by their MCPyV detection. Apart from PD-L1 and PD-1, the TME was further characterized for the expression of CD33, FOXP3 and MxA. Results: We observed PD-1 in 2 of 12 tumors. PD-L1 expression by tumor cells was found in 7 of 8 MCPyV(+) samples and was detected particularly in the periphery. The tumor cells were surrounded by a shield of PD-L1/CD33 immune cells. Expression of PD-L1 by the tumor cells was higher in areas with a denser immune infiltrate. CD33(+) cells without direct tumor contact were PD-L1 negative. Only a low number of FOXP3(+) regulatory T-cells was admixed. Tumor cells of MCPyV(−) samples were mostly PD-L1 negative. Conclusions: Our data demonstrate that PD-L1 expression occurs in tumor and immune cells, in areas in which they are close in contact. Interferon seems to play a role in this interaction. We postulate that PD-L1(+)/CD33(+) cells shield the tumor against attacking PD-1(+) immune cells. Therefore, next to anti-PD-1/PD-L1 antibodies, blockade of CD33 seems to be a promising therapeutic approach. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
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| 18. |
- Mitteldorf, C., et al.
(författare)
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Tumor Microenvironment and Checkpoint Molecules in Primary Cutaneous Diffuse Large B-Cell Lymphoma - New Therapeutic Targets
- 2017
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Ingår i: American Journal of Surgical Pathology. - : Lippincott Williams and Wilkins. - 0147-5185 .- 1532-0979. ; 41:7, s. 998-1004
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Tidskriftsartikel (refereegranskat)abstract
- Programmed death ligand 1 (PD-L1) is expressed by 20% to 57% of systemic diffuse large B cell lymphomas (DLBCLs). PD-L1 expression in primary cutaneous DLBCL (pcDLBCL) has not been studied so far. Sixteen paraffin-embedded tissue samples of pcDLBCL (13 leg type [LT], 3 others [OT]) were investigated for PD-1, PD-L1, and CD33 expression and the cellular composition of the tumor microenvironment, focusing on myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages. Membrane-bound PD-L1 expression by the tumor cells was observed in all samples, albeit to a variable extent (19.9%). As expected, most DLBCL-LT (10 cases) were classified as activated B cell like type, with a higher PD-L1 score (21.9%) compared with that of the germinal center B cell like type (7.7%). The surrounding infiltrate consisted predominately of CD163(+) M2 rather than CD68(+) macrophages (CD68:CD163=1:4 to 6). Moreover, a considerable proportion of CD33(+) MDSCs with PD-L1 coexpression was admixed. Tumor cells expressed CD33 to variable degrees (2% to 60%). The number of MDSCs or M2 macrophages did not correlate with pcDLBCL subtypes LT or OT. T cells were only a minor component of the tumor microenvironment. We propose that PD-L1(+) tumor cells and PD-L1(+) MDSCs shield the tumor against PD-1(+) tumor-infiltrating lymphocytes, consequently leading to inhibition and diminution of tumor-infiltrating lymphocytes. Moreover, we found a polarization to M2 macrophages, which may contribute to the poor prognosis of DLBCL patients. Thus, targeting of tumor cells and MDSCs using anti-PD-1/anti-PD-L1 or anti-CD33 antibodies might be a worthwhile new approach to treat this aggressive form of cutaneous B-cell lymphoma. © 2017 Wolters Kluwer Health, Inc. All rights reserved.
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| 20. |
- Turc, L., et al.
(författare)
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Transmission of foreshock waves through Earth's bow shock
- 2023
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Ingår i: Nature Physics. - : Springer Nature. - 1745-2473 .- 1745-2481. ; 19:1, s. 78-86
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Tidskriftsartikel (refereegranskat)abstract
- The Earth's magnetosphere and its bow shock, which is formed by the interaction of the supersonic solar wind with the terrestrial magnetic field, constitute a rich natural laboratory enabling in situ investigations of universal plasma processes. Under suitable interplanetary magnetic field conditions, a foreshock with intense wave activity forms upstream of the bow shock. So-called 30 s waves, named after their typical period at Earth, are the dominant wave mode in the foreshock and play an important role in modulating the shape of the shock front and affect particle reflection at the shock. These waves are also observed inside the magnetosphere and down to the Earth's surface, but how they are transmitted through the bow shock remains unknown. By combining state-of-the-art global numerical simulations and spacecraft observations, we demonstrate that the interaction of foreshock waves with the shock generates earthward-propagating, fast-mode waves, which reach the magnetosphere. These findings give crucial insight into the interaction of waves with collisionless shocks in general and their impact on the downstream medium.
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| 21. |
- Wollert, Kai C., et al.
(författare)
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Prognostic value of growth-differentiation factor-15 in patients with non-ST-elevation acute coronary syndrome
- 2007
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Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 115:8, s. 962-971
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Growth-differentiation factor-15 (GDF-15) is a member of the transforming growth factor-beta cytokine superfamily that is induced in the heart after ischemia-and-reperfusion injury. Circulating levels of GDF-15 may provide prognostic information in patients with non-ST-elevation acute coronary syndrome. METHODS AND RESULTS: Blood samples were obtained on admission from 2081 patients with acute chest pain and either ST-segment depression or troponin elevation who were included in the Global Utilization of Strategies to Open Occluded Arteries (GUSTO)-IV Non-ST-Elevation Acute Coronary Syndrome trial and from a matching cohort of 429 apparently healthy individuals. GDF-15 levels were determined by immunoradiometric assay. Approximately two thirds of patients presented with GDF-15 levels above the upper limit of normal in healthy controls (1200 ng/L); one third presented with levels >1800 ng/L. Increasing tertiles of GDF-15 were associated with an enhanced risk of death at 1 year (1.5%, 5.0%, and 14.1%; P<0.001). By multiple Cox regression analysis, only the levels of GDF-15 and N-terminal pro-B-type natriuretic peptide, together with age and a history of previous myocardial infarction, contributed independently to 1-year mortality risk. Receiver operating characteristic curve analyses further illustrated that GDF-15 is a strong marker of 1-year mortality risk (area under the curve, 0.757; best cutoff, 1808 ng/L). At this cutoff value, GDF-15 added significant prognostic information in patient subgroups defined by age; gender; time from symptom onset to admission; cardiovascular risk factors; previous cardiovascular disease; and the risk markers ST-segment depression, troponin T, N-terminal pro-B-type natriuretic peptide, C-reactive protein, and creatinine clearance. CONCLUSIONS: GDF-15 is a new biomarker of the risk for death in patients with non-ST-elevation acute coronary syndrome that provides prognostic information beyond that provided by established clinical and biochemical markers.
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