ArticlePloS one2015
Biomarkers of Endothelial Activation Are Associated with Poor Outcome in Critical Illness.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 2 of them syntheses that pooled it.
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Who cites it
69 citing papers in PubMed, 2 syntheses or guidelines pooled it, 120 citations in OpenAlex.
- Exploring the Impact of Extracorporeal Membrane Oxygenation on the Endothelium: A Systematic Review.International journal of molecular sciences · 2024Pooled it
- Value and mechanisms of EEG reactivity in the prognosis of patients with impaired consciousness: a systematic review.Critical care (London, England) · 2018Pooled it
- Concurrent Immune Suppression and Hyperinflammation in Patients With Community-Acquired Pneumonia.Frontiers in immunology · 2020Trial
- Trial
- Endothelial Permeability and Hemostasis in Septic Shock: Results From the ProCESS Trial.Chest · 2017Trial
- Endothelial biomarkers predict kidney and cardiovascular outcomes after acute kidney injury.Clinical kidney journal · 2026Article
- Plasma antioxidant capacity as a predictor of mortality in critically ill patients.Critical care (London, England) · 2026Observational
- Early Dysregulation of Angiopoietin-1 and -2 as a Predictor of Mortality in Critically Ill Burn Patients.Journal of burn care & research : official publication of the American Burn Association · 2026Article
- Mechanisms That Prevent Vascular Leakage During Leukocyte Extravasation.Acta physiologica (Oxford, England) · 2025Review
- Pro- and Anti-Inflammatory Responses and Clinical Outcomes in Critically Ill Patients With Endotheliopathy: A Cohort Study.Acta anaesthesiologica Scandinavica · 2025Article
- Macrophage activation syndrome in Sepsis: from pathogenesis to clinical management.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Review
- Observational
- Angiopoietin-2 is associated with sickle cell complications, including stroke risk, and decreases with hydroxyurea therapy.Blood vessels, thrombosis & hemostasis · 2024Article
- Whole blood ratio ofFrontiers in medicine · 2024Article
- Article
- Immunological responses of septic rats to combination therapy with thymosin α1 and vitamin C.Open life sciences · 2023Article
- Organotypic heterogeneity in microvascular endothelial cell responses in sepsis-a molecular treasure trove and pharmacological Gordian knot.Frontiers in medicine · 2023Review
- MICROVASCULAR ENDOTHELIAL ACTIVATION/DYSFUNCTION AND DYSREGULATION OF THE ANGIOPOIETIN-TIE2 SYSTEM IN THE PATHOGENESIS OF LIFE-THREATENING INFECTIONS.Transactions of the American Clinical and Climatological Association · 2023Article
- Non-Invasive Pulsatile Shear Stress Modifies Endothelial Activation; A Narrative Review.Biomedicines · 2022Review
- Immune and endothelial activation markers and risk stratification of childhood pneumonia in Uganda: A secondary analysis of a prospective cohort study.PLoS medicine · 2022Article
9 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundEndothelial activation plays a role in organ dysfunction in the systemic inflammatory response syndrome (SIRS). Angiopoietin-1 (Ang-1) promotes vascular quiescence while angiopoietin-2 (Ang-2) mediates microvascular leak. Circulating levels of Ang-1 and Ang-2 in patients with SIRS could provide insight on risks for organ dysfunction and death distinct from inflammatory proteins. In this study, we determined if biomarkers of endothelial activation and inflammation exhibit independent associations with poor outcomes in SIRS.
methodsWe studied 943 critically ill patients with SIRS admitted to an Intensive Care Unit (ICU) of an academic medical center. We measured plasma levels of endothelial markers (Ang-1, Ang-2, soluble vascular cell adhesion molecule-1 (sVCAM-1)) and inflammatory markers (interleukin-6 (IL-6), interleukin-8 (IL-8), granulocyte-colony stimulating factor (G-CSF), soluble tumor necrosis factor receptor-1 (sTNFR-1)) within 24 hours of enrollment. We tested for associations between each marker and 28 day mortality, shock, and day 3 sequential organ failure assessment (SOFA) score. For 28 day mortality, we performed sensitivity analysis for those subjects with sepsis and those with sterile inflammation. We used multivariate models to adjust for clinical covariates and determine if associations identified with endothelial activation markers were independent of those observed with inflammatory markers.
resultsHigher levels of all biomarkers were associated with increased 28 day mortality except levels of Ang-1 which were associated with lower mortality. After adjustment for comorbidities and sTNFR-1 concentration, a doubling of Ang-1 concentration was associated with lower 28 day mortality (Odds ratio (OR) = 0.81; p<0.01), shock (OR = 0.82; p<0.001), and SOFA score (β = -0.50; p<0.001), while Ang-2 concentration was associated with increased mortality (OR = 1.55; p<0.001), shock (OR = 1.51; p<0.001), and SOFA score (β = +0.63; p<0.001). sVCAM-1 was not independently associated with SIRS outcomes.
conclusionsIn critically ill patients with SIRS, early measurements of Ang-1 and Ang-2 are associated with death and organ dysfunction independently of simultaneously-measured markers of inflammation.
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