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Metabolites Concentration in Plasma and Heart Tissue in Relation to High Sensitive Cardiac Troponin T Level in Septic Shock Pigs
Elevated circulating cardiac troponin T (cTnT) is frequent in septic shock patients. Signs of myocardial ischemia and myocyte necrosis are not universally present, but the precise mechanism for elevated cTnT is unknown. We investigated plasma and heart tissue metabolites concentration in six septic...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9024493/ https://www.ncbi.nlm.nih.gov/pubmed/35448505 http://dx.doi.org/10.3390/metabo12040319 |
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author | Bollen Pinto, Bernardo Ferrario, Manuela Herpain, Antoine Brunelli, Laura Bendjelid, Karim Carrara, Marta Pastorelli, Roberta |
author_facet | Bollen Pinto, Bernardo Ferrario, Manuela Herpain, Antoine Brunelli, Laura Bendjelid, Karim Carrara, Marta Pastorelli, Roberta |
author_sort | Bollen Pinto, Bernardo |
collection | PubMed |
description | Elevated circulating cardiac troponin T (cTnT) is frequent in septic shock patients. Signs of myocardial ischemia and myocyte necrosis are not universally present, but the precise mechanism for elevated cTnT is unknown. We investigated plasma and heart tissue metabolites concentration in six septic shock (SS) and three sham swine undergoing a protocol of polymicrobial septic shock and resuscitation, in order to highlight possible pathways and biomarkers involved in troponin release (high sensitive cardiac troponin T, hs-cTnT). The animals were divided into two groups: the high cTnT group (n = 3) were pigs showing a significantly higher concentration of cTnT and lactate after resuscitation; the low cTnT group (n = 6, three sham and three septic shock) characterized by a lower value of cTnT and a lactate level < 2 mmol/L. Spearman correlation was assessed on plasma fold-change of cTnT, cytokines (TNF-α and IL-10), and metabolites. Finally, the fold-change between the end of resuscitation and baseline values (Res./BL) of plasma metabolites was used to perform a partial least square discriminant analysis (PLS-DA) with three latent variables. Before building the model, the number of features was reduced by summing up the metabolites of the same class that resulted similarly correlated to cTnT fold-change. Proline and glycine were significantly higher in the high cTnT group at the end of experiment both in the myocardium and plasma analyses. Moreover, plasma proline fold-change was found to be positively correlated with cTnT and cytokine fold-changes, and trans-4-hydroxyproline (t4-OH-Pro) fold-change was positively correlated with cTnT fold-change. The PLS-DA model was able to separate the two groups and, among the first ranked features based on VIP score, we found sugars, t4-OH-Pro, proline, creatinine, total amount of sphingomyelins, and glycine. Proline, t4-OH-Pro, and glycine are very abundant in collagen, and our results may suggest that collagen degradation could represent a possible mechanism contributing to septic myocardial injury. The common phenotype of septic cardiomyopathy could be associated to dysregulated collagen metabolism and/or degradation, further exacerbated by higher inflammation and oxidative stress. |
format | Online Article Text |
id | pubmed-9024493 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-90244932022-04-23 Metabolites Concentration in Plasma and Heart Tissue in Relation to High Sensitive Cardiac Troponin T Level in Septic Shock Pigs Bollen Pinto, Bernardo Ferrario, Manuela Herpain, Antoine Brunelli, Laura Bendjelid, Karim Carrara, Marta Pastorelli, Roberta Metabolites Article Elevated circulating cardiac troponin T (cTnT) is frequent in septic shock patients. Signs of myocardial ischemia and myocyte necrosis are not universally present, but the precise mechanism for elevated cTnT is unknown. We investigated plasma and heart tissue metabolites concentration in six septic shock (SS) and three sham swine undergoing a protocol of polymicrobial septic shock and resuscitation, in order to highlight possible pathways and biomarkers involved in troponin release (high sensitive cardiac troponin T, hs-cTnT). The animals were divided into two groups: the high cTnT group (n = 3) were pigs showing a significantly higher concentration of cTnT and lactate after resuscitation; the low cTnT group (n = 6, three sham and three septic shock) characterized by a lower value of cTnT and a lactate level < 2 mmol/L. Spearman correlation was assessed on plasma fold-change of cTnT, cytokines (TNF-α and IL-10), and metabolites. Finally, the fold-change between the end of resuscitation and baseline values (Res./BL) of plasma metabolites was used to perform a partial least square discriminant analysis (PLS-DA) with three latent variables. Before building the model, the number of features was reduced by summing up the metabolites of the same class that resulted similarly correlated to cTnT fold-change. Proline and glycine were significantly higher in the high cTnT group at the end of experiment both in the myocardium and plasma analyses. Moreover, plasma proline fold-change was found to be positively correlated with cTnT and cytokine fold-changes, and trans-4-hydroxyproline (t4-OH-Pro) fold-change was positively correlated with cTnT fold-change. The PLS-DA model was able to separate the two groups and, among the first ranked features based on VIP score, we found sugars, t4-OH-Pro, proline, creatinine, total amount of sphingomyelins, and glycine. Proline, t4-OH-Pro, and glycine are very abundant in collagen, and our results may suggest that collagen degradation could represent a possible mechanism contributing to septic myocardial injury. The common phenotype of septic cardiomyopathy could be associated to dysregulated collagen metabolism and/or degradation, further exacerbated by higher inflammation and oxidative stress. MDPI 2022-04-02 /pmc/articles/PMC9024493/ /pubmed/35448505 http://dx.doi.org/10.3390/metabo12040319 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 Bollen Pinto, Bernardo Ferrario, Manuela Herpain, Antoine Brunelli, Laura Bendjelid, Karim Carrara, Marta Pastorelli, Roberta Metabolites Concentration in Plasma and Heart Tissue in Relation to High Sensitive Cardiac Troponin T Level in Septic Shock Pigs |
title | Metabolites Concentration in Plasma and Heart Tissue in Relation to High Sensitive Cardiac Troponin T Level in Septic Shock Pigs |
title_full | Metabolites Concentration in Plasma and Heart Tissue in Relation to High Sensitive Cardiac Troponin T Level in Septic Shock Pigs |
title_fullStr | Metabolites Concentration in Plasma and Heart Tissue in Relation to High Sensitive Cardiac Troponin T Level in Septic Shock Pigs |
title_full_unstemmed | Metabolites Concentration in Plasma and Heart Tissue in Relation to High Sensitive Cardiac Troponin T Level in Septic Shock Pigs |
title_short | Metabolites Concentration in Plasma and Heart Tissue in Relation to High Sensitive Cardiac Troponin T Level in Septic Shock Pigs |
title_sort | metabolites concentration in plasma and heart tissue in relation to high sensitive cardiac troponin t level in septic shock pigs |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9024493/ https://www.ncbi.nlm.nih.gov/pubmed/35448505 http://dx.doi.org/10.3390/metabo12040319 |
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