Leha, Andreas

[["dc.bibliographiccitation.firstpage","3086"],["dc.bibliographiccitation.issue","19"],["dc.bibliographiccitation.journal","Cells"],["dc.bibliographiccitation.volume","11"],["dc.contributor.affiliation","Jarausch, Johannes; 1Department of Clinical Chemistry and Interdisciplinary UMG Laboratory, University Medical Center Goettingen, Robert-Koch-Str. 40, 37075 Goettingen, Germany"],["dc.contributor.affiliation","Neuenroth, Lisa; 1Department of Clinical Chemistry and Interdisciplinary UMG Laboratory, University Medical Center Goettingen, Robert-Koch-Str. 40, 37075 Goettingen, Germany"],["dc.contributor.affiliation","Andag, Reiner; 1Department of Clinical Chemistry and Interdisciplinary UMG Laboratory, University Medical Center Goettingen, Robert-Koch-Str. 40, 37075 Goettingen, Germany"],["dc.contributor.affiliation","Leha, Andreas; 3Department of Medical Statistics, University Medical Center Goettingen, Humboldtallee 32, 37073 Goettingen, Germany"],["dc.contributor.affiliation","Fischer, Andreas; 1Department of Clinical Chemistry and Interdisciplinary UMG Laboratory, University Medical Center Goettingen, Robert-Koch-Str. 40, 37075 Goettingen, Germany"],["dc.contributor.affiliation","Asif, Abdul R.; 1Department of Clinical Chemistry and Interdisciplinary UMG Laboratory, University Medical Center Goettingen, Robert-Koch-Str. 40, 37075 Goettingen, Germany"],["dc.contributor.affiliation","Lenz, Christof; 1Department of Clinical Chemistry and Interdisciplinary UMG Laboratory, University Medical Center Goettingen, Robert-Koch-Str. 40, 37075 Goettingen, Germany"],["dc.contributor.affiliation","Eidizadeh, Abass; 1Department of Clinical Chemistry and Interdisciplinary UMG Laboratory, University Medical Center Goettingen, Robert-Koch-Str. 40, 37075 Goettingen, Germany"],["dc.contributor.author","Jarausch, Johannes"],["dc.contributor.author","Neuenroth, Lisa"],["dc.contributor.author","Andag, Reiner"],["dc.contributor.author","Leha, Andreas"],["dc.contributor.author","Fischer, Andreas"],["dc.contributor.author","Asif, Abdul R."],["dc.contributor.author","Lenz, Christof"],["dc.contributor.author","Eidizadeh, Abass"],["dc.contributor.editor","Zhou, Changcheng"],["dc.contributor.editor","Chen, Hong"],["dc.date.accessioned","2022-11-01T10:17:24Z"],["dc.date.available","2022-11-01T10:17:24Z"],["dc.date.issued","2022"],["dc.date.updated","2022-11-11T13:12:33Z"],["dc.description.abstract","Atherosclerosis is an important risk factor in the development of cardiovascular diseases. In addition to increased plasma lipid concentrations, irregular/oscillatory shear stress and inflammatory processes trigger atherosclerosis. Inhibitors of the transcription modulatory bromo- and extra-terminal domain (BET) protein family (BETi) could offer a possible therapeutic approach due to their epigenetic mechanism and anti-inflammatory properties. In this study, the influence of laminar shear stress, inflammation and BETi treatment on human endothelial cells was investigated using global protein expression profiling by ion mobility separation-enhanced data independent acquisition mass spectrometry (IMS-DIA-MS). For this purpose, primary human umbilical cord derived vascular endothelial cells were treated with TNFα to mimic inflammation and exposed to laminar shear stress in the presence or absence of the BRD4 inhibitor JQ1. IMS-DIA-MS detected over 4037 proteins expressed in endothelial cells. Inflammation, shear stress and BETi led to pronounced changes in protein expression patterns with JQ1 having the greatest effect. To our knowledge, this is the first proteomics study on primary endothelial cells, which provides an extensive database for the effects of shear stress, inflammation and BETi on the endothelial proteome."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2022"],["dc.identifier.doi","10.3390/cells11193086"],["dc.identifier.pii","cells11193086"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/116800"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-605"],["dc.publisher","MDPI"],["dc.relation.eissn","2073-4409"],["dc.rights","CC BY 4.0"],["dc.title","Influence of Shear Stress, Inflammation and BRD4 Inhibition on Human Endothelial Cells: A Holistic Proteomic Approach"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","3148"],["dc.bibliographiccitation.issue","14"],["dc.bibliographiccitation.journal","Journal of Clinical Medicine"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Eidizadeh, Abass"],["dc.contributor.author","Fraune, Laura"],["dc.contributor.author","Leha, Andreas"],["dc.contributor.author","Wachter, Rolf"],["dc.contributor.author","Asif, Abdul R."],["dc.contributor.author","Binder, Lutz"],["dc.date.accessioned","2021-08-12T07:46:00Z"],["dc.date.available","2021-08-12T07:46:00Z"],["dc.date.issued","2021"],["dc.description.abstract","Cardiac troponins are crucial for the diagnosis of acute myocardial infarction. Despite known differences in their diagnostic implication, there are no recommendations for only one of the two troponins, cardiac troponin I (cTnI) and troponin T (cTnT) so far. In an everyday routine diagnostic, cTnT (Roche) as well as cTnI (Abbott) were measured in 5667 samples from 3264 patient cases. We investigated the number of identical or discrepant troponin findings. Regarding cTnI, we considered both, sex-dependent and unisex cutoffs. In particular, the number of cTnT positive and cTnI negative results was strikingly high in 14.0% of cTnT positive samples and increases to 23.8% by using sex-specific cTnI cutoffs. This group was considerably greater than the group of cTnI positive and cTnT negative results, also after elimination of patients with an eGFR < 60 mL/min/1.73 m2. Comparing the troponin cases with a dynamic increase or decrease between two measurements, we saw a balanced number of discrepant cases (between cTnT+/cTnI− and cTnT−/cTnI+), which was, however, still present. Using ROC analysis, sex-dependent cutoffs improved sensitivity and specificity of cTnI. This study shows in a large cohort that comparing the two cardiac troponins does not amount to identical analytical results. Consideration of sex-dependent cutoffs may improve sensitivity and specificity."],["dc.description.abstract","Cardiac troponins are crucial for the diagnosis of acute myocardial infarction. Despite known differences in their diagnostic implication, there are no recommendations for only one of the two troponins, cardiac troponin I (cTnI) and troponin T (cTnT) so far. In an everyday routine diagnostic, cTnT (Roche) as well as cTnI (Abbott) were measured in 5667 samples from 3264 patient cases. We investigated the number of identical or discrepant troponin findings. Regarding cTnI, we considered both, sex-dependent and unisex cutoffs. In particular, the number of cTnT positive and cTnI negative results was strikingly high in 14.0% of cTnT positive samples and increases to 23.8% by using sex-specific cTnI cutoffs. This group was considerably greater than the group of cTnI positive and cTnT negative results, also after elimination of patients with an eGFR < 60 mL/min/1.73 m2. Comparing the troponin cases with a dynamic increase or decrease between two measurements, we saw a balanced number of discrepant cases (between cTnT+/cTnI− and cTnT−/cTnI+), which was, however, still present. Using ROC analysis, sex-dependent cutoffs improved sensitivity and specificity of cTnI. This study shows in a large cohort that comparing the two cardiac troponins does not amount to identical analytical results. Consideration of sex-dependent cutoffs may improve sensitivity and specificity."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2021"],["dc.identifier.doi","10.3390/jcm10143148"],["dc.identifier.pii","jcm10143148"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/88596"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-448"],["dc.relation.eissn","2077-0383"],["dc.relation.orgunit","Institut für Klinische Chemie"],["dc.rights","CC BY 4.0"],["dc.title","Inconsistent Findings of Cardiac Troponin T and I in Clinical Routine Diagnostics: Factors of Influence"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2796"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","Cells"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Schnelle, Moritz"],["dc.contributor.author","Leha, Andreas"],["dc.contributor.author","Eidizadeh, Abass"],["dc.contributor.author","Fuhlrott, Katharina"],["dc.contributor.author","Trippel, Tobias D."],["dc.contributor.author","Hashemi, Djawid"],["dc.contributor.author","Toischer, Karl"],["dc.contributor.author","Wachter, Rolf"],["dc.contributor.author","Herrmann-Lingen, Christoph"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Edelmann, Frank"],["dc.contributor.author","Pieske, Burkert"],["dc.contributor.author","Binder, Lutz"],["dc.contributor.editor","Santulli, Gaetano"],["dc.date.accessioned","2021-12-01T09:22:48Z"],["dc.date.available","2021-12-01T09:22:48Z"],["dc.date.issued","2021"],["dc.description.abstract","The pathophysiology of heart failure with preserved ejection fraction (HFpEF) is poorly understood and therapeutic strategies are lacking. This study aimed to identify plasma proteins with pathophysiological relevance in HFpEF and with respect to spironolactone-induced effects. We assessed 92 biomarkers in plasma samples from 386 HFpEF patients—belonging to the Aldo-DHF trial—before (baseline, BL) and after one-year treatment (follow up, FU) with spironolactone (verum) or a placebo. At BL, various biomarkers showed significant associations with the two Aldo-DHF primary end point parameters: 33 with E/e’ and 20 with peak VO2. Ten proteins including adrenomedullin, FGF23 and inflammatory peptides (e.g., TNFRSF11A, TRAILR2) were significantly associated with both parameters, suggesting a role in the clinical HFpEF presentation. For 13 proteins, expression changes from BL to FU were significantly different between verum and placebo. Among them were renin, growth hormone, adrenomedullin and inflammatory proteins (e.g., TNFRSF11A, IL18 and IL4RA), indicating distinct spironolactone-mediated effects. BL levels of five proteins, e.g., inflammatory markers such as CCL17, IL4RA and IL1ra, showed significantly different effects on the instantaneous risk for hospitalization between verum and placebo. This study identified plasma proteins with different implications in HFpEF and following spironolactone treatment. Future studies need to define their precise mechanistic involvement."],["dc.description.abstract","The pathophysiology of heart failure with preserved ejection fraction (HFpEF) is poorly understood and therapeutic strategies are lacking. This study aimed to identify plasma proteins with pathophysiological relevance in HFpEF and with respect to spironolactone-induced effects. We assessed 92 biomarkers in plasma samples from 386 HFpEF patients—belonging to the Aldo-DHF trial—before (baseline, BL) and after one-year treatment (follow up, FU) with spironolactone (verum) or a placebo. At BL, various biomarkers showed significant associations with the two Aldo-DHF primary end point parameters: 33 with E/e’ and 20 with peak VO2. Ten proteins including adrenomedullin, FGF23 and inflammatory peptides (e.g., TNFRSF11A, TRAILR2) were significantly associated with both parameters, suggesting a role in the clinical HFpEF presentation. For 13 proteins, expression changes from BL to FU were significantly different between verum and placebo. Among them were renin, growth hormone, adrenomedullin and inflammatory proteins (e.g., TNFRSF11A, IL18 and IL4RA), indicating distinct spironolactone-mediated effects. BL levels of five proteins, e.g., inflammatory markers such as CCL17, IL4RA and IL1ra, showed significantly different effects on the instantaneous risk for hospitalization between verum and placebo. This study identified plasma proteins with different implications in HFpEF and following spironolactone treatment. Future studies need to define their precise mechanistic involvement."],["dc.identifier.doi","10.3390/cells10102796"],["dc.identifier.pii","cells10102796"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/94485"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-478"],["dc.publisher","MDPI"],["dc.relation.eissn","2073-4409"],["dc.rights","Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/)."],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0/"],["dc.title","Plasma Biomarker Profiling in Heart Failure Patients with Preserved Ejection Fraction before and after Spironolactone Treatment: Results from the Aldo-DHF Trial"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","ehf2.14167"],["dc.bibliographiccitation.journal","ESC Heart Failure"],["dc.contributor.author","Eidizadeh, Abass"],["dc.contributor.author","Schnelle, Moritz"],["dc.contributor.author","Leha, Andreas"],["dc.contributor.author","Edelmann, Frank"],["dc.contributor.author","Nolte, Kathleen"],["dc.contributor.author","Werhahn, Stefanie Maria"],["dc.contributor.author","Binder, Lutz"],["dc.contributor.author","Wachter, Rolf"],["dc.date.accessioned","2022-11-01T10:16:34Z"],["dc.date.available","2022-11-01T10:16:34Z"],["dc.date.issued","2022"],["dc.identifier.doi","10.1002/ehf2.14167"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/116600"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-605"],["dc.relation.eissn","2055-5822"],["dc.relation.issn","2055-5822"],["dc.title","Biomarker profiles in heart failure with preserved vs. reduced ejection fraction: results from the DIAST‐CHF study"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]