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Influence of shear stress, inflammation and BRD4 inhibition on human endothelial cells: a holistic proteomic approach
Zitieren Sie bitte immer diese URN: urn:nbn:de:bvb:20-opus-289872
- 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 humanAtherosclerosis 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.…
Autor(en): | Johannes Jarausch, Lisa Neuenroth, Reiner Andag, Andreas Leha, Andreas Fischer, Abdul R. Asif, Christof Lenz, Abass Eidizadeh |
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URN: | urn:nbn:de:bvb:20-opus-289872 |
Dokumentart: | Artikel / Aufsatz in einer Zeitschrift |
Institute der Universität: | Medizinische Fakultät / Medizinische Klinik und Poliklinik I |
Sprache der Veröffentlichung: | Englisch |
Titel des übergeordneten Werkes / der Zeitschrift (Englisch): | Cells |
ISSN: | 2073-4409 |
Erscheinungsjahr: | 2022 |
Band / Jahrgang: | 11 |
Heft / Ausgabe: | 19 |
Aufsatznummer: | 3086 |
Originalveröffentlichung / Quelle: | Cells (2022) 11:19, 3086. https://doi.org/10.3390/cells11193086 |
DOI: | https://doi.org/10.3390/cells11193086 |
Allgemeine fachliche Zuordnung (DDC-Klassifikation): | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit | |
Freie Schlagwort(e): | BET Inhibitor; BRD4; DIA-MS; HUVEC; JQ1; atherosclerosis; endothelial; proteomic; shear stress |
Datum der Freischaltung: | 12.10.2023 |
Datum der Erstveröffentlichung: | 30.09.2022 |
Lizenz (Deutsch): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |