Dataset Information

Thrombomodulin, Plasminogen Activator Inhibitor-1 and Protein C Levels, and Organ Dysfunction in Sepsis.

ABSTRACT: Since endothelial function is closely related to organ dysfunction in sepsis and the relationship among endothelial injury, organ dysfunction, and other biomarkers remains unclear, we aimed to evaluate the correlation among endothelial injury, organ dysfunction, and several biomarkers in patients with sepsis.

Design

This was a retrospective observational study.

Setting

The study was conducted in a university hospital with 14 mixed ICU beds.

Patients

ICU patients with sepsis from June 2011 to December 2017 were enrolled in this study.

Interventions

Endothelial biomarkers (soluble thrombomodulin, plasminogen activator inhibitor-1, and protein C) and markers of inflammation and coagulation were evaluated during the ICU stay. Sequential Organ Failure Assessment scores were assessed for 7 days after ICU admission to determine organ dysfunction. Variables were compared among five stratified groups according to the Sequential Organ Failure Assessment score (0-2, 3-5, 6-8, 9-12, and 13-24). Regression analysis and 95% CIs were used to evaluate trends in biomarkers.

Measurements and main results

The patients were divided into five stratified groups (Sequential Organ Failure Assessment 0-2, n = 159 [20.5%]; Sequential Organ Failure Assessment 3-5, n = 296 [38.2%]; Sequential Organ Failure Assessment 6-8, n = 182 [23.5%]; Sequential Organ Failure Assessment 9-12, n = 75 [9.7%]; Sequential Organ Failure Assessment 13-24, n = 31 [4.0%]). Protein C activity was significantly correlated with the severity of organ dysfunction. It was lower on day 1, increased upon successful treatment, and was significantly higher in groups with lower Sequential Organ Failure Assessment scores.

Conclusions

Trends and activity of protein C were superior in predicting organ dysfunction compared with other endothelial biomarkers. Monitoring the level of protein C activity is an ideal tool to monitor organ dysfunctions in patients with sepsis.

SUBMITTER: Katayama S

PROVIDER: S-EPMC7063963 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Publications

Thrombomodulin, Plasminogen Activator Inhibitor-1 and Protein C Levels, and Organ Dysfunction in Sepsis.

Katayama Shinshu S Koyama Kansuke K Shima Jun J Tonai Ken K Goto Yuya Y Koinuma Toshitaka T Nunomiya Shin S

Critical care explorations 20190523 5

Since endothelial function is closely related to organ dysfunction in sepsis and the relationship among endothelial injury, organ dysfunction, and other biomarkers remains unclear, we aimed to evaluate the correlation among endothelial injury, organ dysfunction, and several biomarkers in patients with sepsis.<h4>Design</h4>This was a retrospective observational study.<h4>Setting</h4>The study was conducted in a university hospital with 14 mixed ICU beds.<h4>Patients</h4>ICU patients with sepsis ...[more]

PMID: 32166258

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Project description:BackgroundRecessive mutations in WRN gene eliminate WRN protein function (helicase) and cause Werner syndrome. One of the most important clinical features of Werner syndrome patients are the premature onset and accelerated atherosclerosis process. Studies carried out on polymorphic WRN locus have shown that the alleles 1367R and 1074L confer protection for cardiovascular disease. Given that the levels of plasminogen activator inhibitor type 1 (PAI-1) were found to be significantly increased in Werner syndrome patients, is quiet possible that PAI-1 expression could be under regulation of WRN helicase. Therefore the purpose of this work was to evaluate the role of WRN polymorphism in modulating the expression of PAI-1.MethodsIn order to accomplish our aim, an array of primary cultured fibroblasts from normal adult donors was genotyped for polymorphisms of both the WRN and PAI-1 loci. In addition, steady state levels of WRN and PAI-1 were measured by semi-quantitative RT-PCR assays in such cultures. To search for the potential relationship between the lack of WRN protein and PAI-1 expression, heterozygous cultures of fibroblasts (1367RC/1074LF; WRN genotype) were treated with a molecule of interference RNA against WRN messenger RNA (mRNA).ResultsWe found that, carriers of 1367R and 1074L alleles of WRN shown to have low amounts of PAI-1 in plasma (7.56 +/- 5.02), as compared with carriers of 1367C and 1074F alleles (16.09 +/- 6.03). Moreover, fibroblasts from carriers with these alleles had low expression levels of PAI-1 mRNA. The treatment of heterozygous primary fibroblast cultures (1367RC/1074LF; WRN genotype) with iRNA against WRN mRNA caused PAI-1 overexpression. Treatment with normal PAI-1 inducers (TGFbeta, TNFalpha, or insulin) in these cultures and from those with genotypes 1367CC/1074FF and 1367RR/1074FL resulted in a genotype-dependent PAI-1 expression level.ConclusionOur results suggest that polymorphisms in the WRN gene might have a significant role regulating PAI-1 levels in healthy individuals and "normal states" as well as acute or chronic stress, obesity, aging, acute inflammation, among others, where characteristic high levels of insulin, TNF alpha and TGFbeta, could favor PAI-1 high levels in carriers with polymorphic variants (C and F alleles), beyond the levels reached by carriers with other alleles (R and L alleles).

Dataset Information

Thrombomodulin, Plasminogen Activator Inhibitor-1 and Protein C Levels, and Organ Dysfunction in Sepsis.

Design

Setting

Patients

Interventions

Measurements and main results

Conclusions

Publications

Thrombomodulin, Plasminogen Activator Inhibitor-1 and Protein C Levels, and Organ Dysfunction in Sepsis.

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