In-vitro and in-silico evidence for oxidative stress as drivers for RDW

被引：23

作者：

Joosse, Huibert-Jan ^{[1
]}

van Oirschot, Brigitte A. A. ^{[1
]}

Kooijmans, Sander A. A. ^{[1
]}

Hoefer, Imo E. E. ^{[1
]}

van Wijk, Richard A. H. ^{[1
]}

Huisman, Albert ^{[1
]}

van Solinge, Wouter W. W. ^{[1
]}

Haitjema, Saskia ^{[1
]}

机构：

[1] Univ Utrecht, Univ Med Ctr Utrecht, Cent Diagnost Lab, Utrecht, Netherlands

来源：

SCIENTIFIC REPORTS | 2023年 / 13卷 / 01期

基金：

荷兰研究理事会;

关键词：

CELL DISTRIBUTION WIDTH; HEART-FAILURE;

D O I：

10.1038/s41598-023-36514-5

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：9

共 31 条

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