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In-vitro and in-silico evidence for oxidative stress as drivers for RDW
Red blood cell distribution width (RDW) is a biomarker associated with a variety of clinical outcomes. While anemia and subclinical inflammation have been posed as underlying pathophysiology, it is unclear what mechanisms underlie these assocations. Hence, we aimed to unravel the mechanisms in silic...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10247684/ https://www.ncbi.nlm.nih.gov/pubmed/37286717 http://dx.doi.org/10.1038/s41598-023-36514-5 |
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author | Joosse, Huibert-Jan van Oirschot, Brigitte A. Kooijmans, Sander A. A. Hoefer, Imo E. van Wijk, Richard A. H. Huisman, Albert van Solinge, Wouter W. Haitjema, Saskia |
author_facet | Joosse, Huibert-Jan van Oirschot, Brigitte A. Kooijmans, Sander A. A. Hoefer, Imo E. van Wijk, Richard A. H. Huisman, Albert van Solinge, Wouter W. Haitjema, Saskia |
author_sort | Joosse, Huibert-Jan |
collection | PubMed |
description | Red blood cell distribution width (RDW) is a biomarker associated with a variety of clinical outcomes. While anemia and subclinical inflammation have been posed as underlying pathophysiology, it is unclear what mechanisms underlie these assocations. Hence, we aimed to unravel the mechanisms in silico using a large clinical dataset and validate our findings in vitro. We retrieved complete blood counts (CBC) from 1,403,663 measurements from the Utrecht Patient Oriented Database, to model RDW using gradient boosting regression. We performed (sex-stratified) analyses in patients with anemia, patients younger/older than 50 and validation across platforms and care settings. We then validated our hypothesis regarding oxidative stress using an in vitro approach. Only percentage microcytic (pMIC) and macrocytic (pMAC) erythrocytes and mean corpuscular volume were most important in modelling RDW (RMSE = 0.40, R(2) = 0.96). Subgroup analyses and validation confirmed our findings. In vitro induction of oxidative stress underscored our results, namely increased RDW and decreased erythrocyte volume, yet no vesiculation was observed. We found that erythrocyte size, especially pMIC, is most informative in predicting RDW, but no role for anemia or inflammation. Oxidative stress affecting the size of the erythrocytes may play a role in the association between RDW and clinical outcomes. |
format | Online Article Text |
id | pubmed-10247684 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-102476842023-06-09 In-vitro and in-silico evidence for oxidative stress as drivers for RDW Joosse, Huibert-Jan van Oirschot, Brigitte A. Kooijmans, Sander A. A. Hoefer, Imo E. van Wijk, Richard A. H. Huisman, Albert van Solinge, Wouter W. Haitjema, Saskia Sci Rep Article Red blood cell distribution width (RDW) is a biomarker associated with a variety of clinical outcomes. While anemia and subclinical inflammation have been posed as underlying pathophysiology, it is unclear what mechanisms underlie these assocations. Hence, we aimed to unravel the mechanisms in silico using a large clinical dataset and validate our findings in vitro. We retrieved complete blood counts (CBC) from 1,403,663 measurements from the Utrecht Patient Oriented Database, to model RDW using gradient boosting regression. We performed (sex-stratified) analyses in patients with anemia, patients younger/older than 50 and validation across platforms and care settings. We then validated our hypothesis regarding oxidative stress using an in vitro approach. Only percentage microcytic (pMIC) and macrocytic (pMAC) erythrocytes and mean corpuscular volume were most important in modelling RDW (RMSE = 0.40, R(2) = 0.96). Subgroup analyses and validation confirmed our findings. In vitro induction of oxidative stress underscored our results, namely increased RDW and decreased erythrocyte volume, yet no vesiculation was observed. We found that erythrocyte size, especially pMIC, is most informative in predicting RDW, but no role for anemia or inflammation. Oxidative stress affecting the size of the erythrocytes may play a role in the association between RDW and clinical outcomes. Nature Publishing Group UK 2023-06-07 /pmc/articles/PMC10247684/ /pubmed/37286717 http://dx.doi.org/10.1038/s41598-023-36514-5 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Joosse, Huibert-Jan van Oirschot, Brigitte A. Kooijmans, Sander A. A. Hoefer, Imo E. van Wijk, Richard A. H. Huisman, Albert van Solinge, Wouter W. Haitjema, Saskia In-vitro and in-silico evidence for oxidative stress as drivers for RDW |
title | In-vitro and in-silico evidence for oxidative stress as drivers for RDW |
title_full | In-vitro and in-silico evidence for oxidative stress as drivers for RDW |
title_fullStr | In-vitro and in-silico evidence for oxidative stress as drivers for RDW |
title_full_unstemmed | In-vitro and in-silico evidence for oxidative stress as drivers for RDW |
title_short | In-vitro and in-silico evidence for oxidative stress as drivers for RDW |
title_sort | in-vitro and in-silico evidence for oxidative stress as drivers for rdw |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10247684/ https://www.ncbi.nlm.nih.gov/pubmed/37286717 http://dx.doi.org/10.1038/s41598-023-36514-5 |
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