A non-lethal traumatic/hemorrhagic insult strongly modulates the compartment-specific PAI-1 response in the subsequent polymicrobial sepsis.

<h4>Introduction</h4>Plasminogen activator inhibitor 1 (PAI-1) is a key factor in trauma- and sepsis-induced coagulopathy. We examined how trauma-hemorrhage (TH) modulates PAI-1 responses in subsequent cecal ligation and puncture (CLP)-induced sepsis, and the association of PAI-1 with se...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Pierre Raeven, Alma Salibasic, Susanne Drechsler, Katrin Maria Weixelbaumer, Mohammad Jafarmadar, Martijn van Griensven, Soheyl Bahrami, Marcin Filip Osuchowski
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/738315d5776e4f0a99738fbe4536ea95
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:738315d5776e4f0a99738fbe4536ea95
record_format	dspace
spelling	oai:doaj.org-article:738315d5776e4f0a99738fbe4536ea952021-11-18T07:58:11ZA non-lethal traumatic/hemorrhagic insult strongly modulates the compartment-specific PAI-1 response in the subsequent polymicrobial sepsis.1932-620310.1371/journal.pone.0055467https://doaj.org/article/738315d5776e4f0a99738fbe4536ea952013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23408987/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Introduction</h4>Plasminogen activator inhibitor 1 (PAI-1) is a key factor in trauma- and sepsis-induced coagulopathy. We examined how trauma-hemorrhage (TH) modulates PAI-1 responses in subsequent cecal ligation and puncture (CLP)-induced sepsis, and the association of PAI-1 with septic outcomes.<h4>Methods</h4>Mice underwent TH and CLP 48 h later in three separate experiments. In experiment 1, mice were sacrificed pre- and post-CLP to characterize the trajectory of PAI-1 in plasma (protein) and tissues (mRNA). Post-CLP dynamics in TH-CLP (this study) and CLP-Only mice (prior study) were then compared for modulatory effects of TH. In experiment 2, to relate PAI-1 changes to outcome, mice underwent TH-CLP and were sampled daily and followed for 14 days to compare non-survivors (DEAD) and survivors (SUR). In experiment 3, plasma and tissue PAI-1 expression were compared between mice predicted to die (P-DIE) and to live (P-LIVE).<h4>Results</h4>In experiment 1, an early post-TH rise of circulating PAI-1 was contrasted by a delayed (post-TH) decrease of PAI-1 mRNA in organs. In the post-CLP phase, profiles of circulating PAI-1 were similar between TH-CLP and CLP-Only mice. Conversely, PAI-1 mRNA declined in the liver and heart of TH-CLP mice versus CLP-Only. In experiment 2, there were no DEAD/SUR differences in circulating PAI-1 prior to CLP. Post-CLP, circulating PAI-1 in DEAD was 2-4-fold higher than in SUR. PAI-1 increase heralded septic deaths up to 48 h prior but DEAD/SUR thrombomodulin (endothelial injury marker) levels were identical. In experiment 3, levels of circulating PAI-1 and its hepatic gene expression were higher in P-DIE versus P-LIVE mice and those increases closely correlated with liver dysfunction.<h4>Conclusions</h4>Trauma modulated septic PAI-1 responses in a compartment-specific fashion. Only post-CLP increases in circulating PAI-1 predicted septic outcomes. In posttraumatic sepsis, pre-lethal release of PAI-1 was mostly of hepatic origin and was independent of endothelial injury.Pierre RaevenAlma SalibasicSusanne DrechslerKatrin Maria WeixelbaumerMohammad JafarmadarMartijn van GriensvenSoheyl BahramiMarcin Filip OsuchowskiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 2, p e55467 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Pierre Raeven Alma Salibasic Susanne Drechsler Katrin Maria Weixelbaumer Mohammad Jafarmadar Martijn van Griensven Soheyl Bahrami Marcin Filip Osuchowski A non-lethal traumatic/hemorrhagic insult strongly modulates the compartment-specific PAI-1 response in the subsequent polymicrobial sepsis.
description	<h4>Introduction</h4>Plasminogen activator inhibitor 1 (PAI-1) is a key factor in trauma- and sepsis-induced coagulopathy. We examined how trauma-hemorrhage (TH) modulates PAI-1 responses in subsequent cecal ligation and puncture (CLP)-induced sepsis, and the association of PAI-1 with septic outcomes.<h4>Methods</h4>Mice underwent TH and CLP 48 h later in three separate experiments. In experiment 1, mice were sacrificed pre- and post-CLP to characterize the trajectory of PAI-1 in plasma (protein) and tissues (mRNA). Post-CLP dynamics in TH-CLP (this study) and CLP-Only mice (prior study) were then compared for modulatory effects of TH. In experiment 2, to relate PAI-1 changes to outcome, mice underwent TH-CLP and were sampled daily and followed for 14 days to compare non-survivors (DEAD) and survivors (SUR). In experiment 3, plasma and tissue PAI-1 expression were compared between mice predicted to die (P-DIE) and to live (P-LIVE).<h4>Results</h4>In experiment 1, an early post-TH rise of circulating PAI-1 was contrasted by a delayed (post-TH) decrease of PAI-1 mRNA in organs. In the post-CLP phase, profiles of circulating PAI-1 were similar between TH-CLP and CLP-Only mice. Conversely, PAI-1 mRNA declined in the liver and heart of TH-CLP mice versus CLP-Only. In experiment 2, there were no DEAD/SUR differences in circulating PAI-1 prior to CLP. Post-CLP, circulating PAI-1 in DEAD was 2-4-fold higher than in SUR. PAI-1 increase heralded septic deaths up to 48 h prior but DEAD/SUR thrombomodulin (endothelial injury marker) levels were identical. In experiment 3, levels of circulating PAI-1 and its hepatic gene expression were higher in P-DIE versus P-LIVE mice and those increases closely correlated with liver dysfunction.<h4>Conclusions</h4>Trauma modulated septic PAI-1 responses in a compartment-specific fashion. Only post-CLP increases in circulating PAI-1 predicted septic outcomes. In posttraumatic sepsis, pre-lethal release of PAI-1 was mostly of hepatic origin and was independent of endothelial injury.
format	article
author	Pierre Raeven Alma Salibasic Susanne Drechsler Katrin Maria Weixelbaumer Mohammad Jafarmadar Martijn van Griensven Soheyl Bahrami Marcin Filip Osuchowski
author_facet	Pierre Raeven Alma Salibasic Susanne Drechsler Katrin Maria Weixelbaumer Mohammad Jafarmadar Martijn van Griensven Soheyl Bahrami Marcin Filip Osuchowski
author_sort	Pierre Raeven
title	A non-lethal traumatic/hemorrhagic insult strongly modulates the compartment-specific PAI-1 response in the subsequent polymicrobial sepsis.
title_short	A non-lethal traumatic/hemorrhagic insult strongly modulates the compartment-specific PAI-1 response in the subsequent polymicrobial sepsis.
title_full	A non-lethal traumatic/hemorrhagic insult strongly modulates the compartment-specific PAI-1 response in the subsequent polymicrobial sepsis.
title_fullStr	A non-lethal traumatic/hemorrhagic insult strongly modulates the compartment-specific PAI-1 response in the subsequent polymicrobial sepsis.
title_full_unstemmed	A non-lethal traumatic/hemorrhagic insult strongly modulates the compartment-specific PAI-1 response in the subsequent polymicrobial sepsis.
title_sort	non-lethal traumatic/hemorrhagic insult strongly modulates the compartment-specific pai-1 response in the subsequent polymicrobial sepsis.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/738315d5776e4f0a99738fbe4536ea95
work_keys_str_mv	AT pierreraeven anonlethaltraumatichemorrhagicinsultstronglymodulatesthecompartmentspecificpai1responseinthesubsequentpolymicrobialsepsis AT almasalibasic anonlethaltraumatichemorrhagicinsultstronglymodulatesthecompartmentspecificpai1responseinthesubsequentpolymicrobialsepsis AT susannedrechsler anonlethaltraumatichemorrhagicinsultstronglymodulatesthecompartmentspecificpai1responseinthesubsequentpolymicrobialsepsis AT katrinmariaweixelbaumer anonlethaltraumatichemorrhagicinsultstronglymodulatesthecompartmentspecificpai1responseinthesubsequentpolymicrobialsepsis AT mohammadjafarmadar anonlethaltraumatichemorrhagicinsultstronglymodulatesthecompartmentspecificpai1responseinthesubsequentpolymicrobialsepsis AT martijnvangriensven anonlethaltraumatichemorrhagicinsultstronglymodulatesthecompartmentspecificpai1responseinthesubsequentpolymicrobialsepsis AT soheylbahrami anonlethaltraumatichemorrhagicinsultstronglymodulatesthecompartmentspecificpai1responseinthesubsequentpolymicrobialsepsis AT marcinfiliposuchowski anonlethaltraumatichemorrhagicinsultstronglymodulatesthecompartmentspecificpai1responseinthesubsequentpolymicrobialsepsis AT pierreraeven nonlethaltraumatichemorrhagicinsultstronglymodulatesthecompartmentspecificpai1responseinthesubsequentpolymicrobialsepsis AT almasalibasic nonlethaltraumatichemorrhagicinsultstronglymodulatesthecompartmentspecificpai1responseinthesubsequentpolymicrobialsepsis AT susannedrechsler nonlethaltraumatichemorrhagicinsultstronglymodulatesthecompartmentspecificpai1responseinthesubsequentpolymicrobialsepsis AT katrinmariaweixelbaumer nonlethaltraumatichemorrhagicinsultstronglymodulatesthecompartmentspecificpai1responseinthesubsequentpolymicrobialsepsis AT mohammadjafarmadar nonlethaltraumatichemorrhagicinsultstronglymodulatesthecompartmentspecificpai1responseinthesubsequentpolymicrobialsepsis AT martijnvangriensven nonlethaltraumatichemorrhagicinsultstronglymodulatesthecompartmentspecificpai1responseinthesubsequentpolymicrobialsepsis AT soheylbahrami nonlethaltraumatichemorrhagicinsultstronglymodulatesthecompartmentspecificpai1responseinthesubsequentpolymicrobialsepsis AT marcinfiliposuchowski nonlethaltraumatichemorrhagicinsultstronglymodulatesthecompartmentspecificpai1responseinthesubsequentpolymicrobialsepsis
_version_	1718422673458987008

A non-lethal traumatic/hemorrhagic insult strongly modulates the compartment-specific PAI-1 response in the subsequent polymicrobial sepsis.

Ejemplares similares