AI Article Synopsis
- PAI-1 is crucial in understanding coagulopathy arising from trauma and sepsis, and this study focuses on how trauma-hemorrhage affects PAI-1 levels in septic situations.
- The research involved experiments on mice, comparing PAI-1 levels in plasma and tissues before and after a cecal ligation and puncture (CLP) procedure to assess outcomes for survivors and non-survivors.
- Findings showed that trauma-induced changes in PAI-1 are compartment-specific and that elevated levels of circulating PAI-1 post-CLP could predict septic deaths, highlighting the significance of monitoring PAI-1 in trauma and sepsis management.
Article Abstract
Introduction: 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.
Methods: 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).
Results: 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.
Conclusions: 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.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3568129 | PMC |
| http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0055467 | PLOS |
Publication Analysis
Top Keywords
Similar Publications
Intermittent low-intensity and moderate-intensity exercise effects on cognition in community-dwelling older adults: a pilot study exploring biological mechanisms.
Front Aging Neurosci
October 2024
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States.
Article Synopsis
- The study investigated how 6 months of intermittent exercise affects cognitive function in older adults, comparing low-intensity movement (LIM) and moderate-intensity aerobic exercise (AE).
- Results showed that LIM improved learning and memory, while AE enhanced executive functioning, indicating different cognitive benefits from each type of exercise.
- Neuroimaging revealed that changes in brain structure and certain inflammatory markers correlated with cognitive improvements, underlining the distinct advantages of both LIM and AE in older populations.
Senescent Syncytiotrophoblast Secretion During Early Onset Preeclampsia.
Hypertension
October 2024
Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany (O.N., D.S.V., J.U., H.B., A.F., N.H., K.K., S.K., D.N.M., R.D., F.H.).
Background: Preeclampsia is a severe hypertensive disorder in pregnancy that causes preterm delivery, maternal and fetal morbidity, mortality, and life-long sequelae. Understanding the pathogenesis of preeclampsia is a critical first step toward protecting mother and child from this syndrome and increased risk of cardiovascular disease later in life. However, effective early predictive tests and therapies for preeclampsia are scarce.
View Article and Find Full Text PDFOral squamous cell carcinomas drive monocytes into immunosuppressive CD25CD163CD206 macrophages.
Oral Oncol
December 2024
Department of Immunology, Ophthalmology and ORL, School of Medicine, Complutense University of Madrid, Pza Ramon y Cajal, s/n, 28040 Madrid, Spain. Electronic address:
Article Synopsis
- Tumor-associated macrophages (TAMs) play a significant role in the tumor microenvironment of oral squamous cell carcinomas (OSCCs) and primarily originate from circulating monocytes that differentiate locally.
- Research showed that cell culture media from OSCC cell lines, H413 and TR146, encourages monocytes to become M2 macrophages, which are characterized by high CD163 and CD206 expression and low levels of activation markers.
- Additionally, the study identified specific soluble proteins in the media that promote this differentiation and linked it to an immunosuppressive profile that hinders T cell activation, shedding light on how OSCCs support tumor growth by altering immune cell behavior.
Unlabelled: Platelets promote tumor metastasis by several mechanisms. Platelet-tumor cell interactions induce the release of platelet cytokines, chemokines, and other factors that promote tumor cell epithelial-mesenchymal transition and invasion, granulocyte recruitment to circulating tumor cells (CTCs), and adhesion of CTCs to the endothelium, assisting in their extravasation at metastatic sites. Previous studies have shown that platelet activation in the context of thrombus formation requires the Class IA PI 3-kinase PI3Kβ.
View Article and Find Full Text PDFThe influence of 4G/5G polymorphism in the plasminogen-activator-inhibitor-1 promoter on COVID-19 severity and endothelial dysfunction.
Front Immunol
September 2024
Department of Research Support Utilizing Bioresource Bank, Graduate School of Medicine, Juntendo University, Tokyo, Japan.
Article Synopsis
- PAI-1 is associated with blood clotting issues and endothelial dysfunction in severe COVID-19, and certain genetic variations can affect its expression.
- Clinical studies on COVID-19 patients found that while comorbidities didn’t correlate with specific genotypes, the 4G/5G polymorphism showed differences in fibrinolytic factors and IL-1β levels.
- The 4G4G genotype was linked to high PAI-1 levels and suppressed fibrinolysis, while inflammation-related endothelial dysfunction was a risk for those with the 5G5G genotype.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!