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Plasma Mitochondrial DNA and Necroptosis as Prognostic Indicators in Critically Ill Patients with Sepsis

Mitochondrial DNA (mtDNA) has been identified as a biomarker for predicting sepsis mortality. Although preclinical studies suggested that necroptosis could explain the mechanistic link of mtDNA in sepsis, this is not yet evident in patients with sepsis. This study evaluated the association between m...

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Autores principales: Choi, Hayoung, Yoo, Hongseok, Lee, Jin Young, Park, Junseon, Jeon, Kyeongman
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9598411/
https://www.ncbi.nlm.nih.gov/pubmed/36289650
http://dx.doi.org/10.3390/biomedicines10102386
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author Choi, Hayoung
Yoo, Hongseok
Lee, Jin Young
Park, Junseon
Jeon, Kyeongman
author_facet Choi, Hayoung
Yoo, Hongseok
Lee, Jin Young
Park, Junseon
Jeon, Kyeongman
author_sort Choi, Hayoung
collection PubMed
description Mitochondrial DNA (mtDNA) has been identified as a biomarker for predicting sepsis mortality. Although preclinical studies suggested that necroptosis could explain the mechanistic link of mtDNA in sepsis, this is not yet evident in patients with sepsis. This study evaluated the association between mtDNA and essential necroptosis mediators in prospectively enrolled patients with sepsis. Plasma mtDNA copy number was measured using quantitative PCR assay and necroptosis mediators, including receptor-interacting protein kinase-3 (RIPK3), mixed lineage domain-like pseudokinase (MLKL), and high-mobility group box 1 (HMGB1), were measured by ELISA. Receiver operating characteristic (ROC) analysis was conducted to evaluate the predictive ability of mtDNA copy number as a predictor of hospital mortality. Among the 142 patients with sepsis, the mtDNA copy number was significantly higher in non-survivors than in survivors (median, 4040 copies/µL vs. 2585 copies/µL; p < 0.001), and the area under the ROC curve was 0.73 (95% CI, 0.64–0.82) for the relationship between mtDNA and hospital mortality. Furthermore, the correlation between mtDNA copy number and each necroptosis mediator was excellent (p < 0.001 for all): RIPK3 (r = 0.803), MLKL (r = 0.897), and HMGB1 (r = 0.603). The plasma mtDNA copy number was highly correlated with essential necroptosis mediators, suggesting that mtDNA propagates necroptosis and increases sepsis mortality.
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spelling pubmed-95984112022-10-27 Plasma Mitochondrial DNA and Necroptosis as Prognostic Indicators in Critically Ill Patients with Sepsis Choi, Hayoung Yoo, Hongseok Lee, Jin Young Park, Junseon Jeon, Kyeongman Biomedicines Article Mitochondrial DNA (mtDNA) has been identified as a biomarker for predicting sepsis mortality. Although preclinical studies suggested that necroptosis could explain the mechanistic link of mtDNA in sepsis, this is not yet evident in patients with sepsis. This study evaluated the association between mtDNA and essential necroptosis mediators in prospectively enrolled patients with sepsis. Plasma mtDNA copy number was measured using quantitative PCR assay and necroptosis mediators, including receptor-interacting protein kinase-3 (RIPK3), mixed lineage domain-like pseudokinase (MLKL), and high-mobility group box 1 (HMGB1), were measured by ELISA. Receiver operating characteristic (ROC) analysis was conducted to evaluate the predictive ability of mtDNA copy number as a predictor of hospital mortality. Among the 142 patients with sepsis, the mtDNA copy number was significantly higher in non-survivors than in survivors (median, 4040 copies/µL vs. 2585 copies/µL; p < 0.001), and the area under the ROC curve was 0.73 (95% CI, 0.64–0.82) for the relationship between mtDNA and hospital mortality. Furthermore, the correlation between mtDNA copy number and each necroptosis mediator was excellent (p < 0.001 for all): RIPK3 (r = 0.803), MLKL (r = 0.897), and HMGB1 (r = 0.603). The plasma mtDNA copy number was highly correlated with essential necroptosis mediators, suggesting that mtDNA propagates necroptosis and increases sepsis mortality. MDPI 2022-09-25 /pmc/articles/PMC9598411/ /pubmed/36289650 http://dx.doi.org/10.3390/biomedicines10102386 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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/).
spellingShingle Article
Choi, Hayoung
Yoo, Hongseok
Lee, Jin Young
Park, Junseon
Jeon, Kyeongman
Plasma Mitochondrial DNA and Necroptosis as Prognostic Indicators in Critically Ill Patients with Sepsis
title Plasma Mitochondrial DNA and Necroptosis as Prognostic Indicators in Critically Ill Patients with Sepsis
title_full Plasma Mitochondrial DNA and Necroptosis as Prognostic Indicators in Critically Ill Patients with Sepsis
title_fullStr Plasma Mitochondrial DNA and Necroptosis as Prognostic Indicators in Critically Ill Patients with Sepsis
title_full_unstemmed Plasma Mitochondrial DNA and Necroptosis as Prognostic Indicators in Critically Ill Patients with Sepsis
title_short Plasma Mitochondrial DNA and Necroptosis as Prognostic Indicators in Critically Ill Patients with Sepsis
title_sort plasma mitochondrial dna and necroptosis as prognostic indicators in critically ill patients with sepsis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9598411/
https://www.ncbi.nlm.nih.gov/pubmed/36289650
http://dx.doi.org/10.3390/biomedicines10102386
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