Early Dysregulation of Angiopoietin-1 and -2 as a Predictor of Mortality in Critically Ill Burn Patients

Sep 29, 2026

Shock-induced endothelial dysfunction is central to burn pathophysiology, where degradation of the endothelial glycocalyx promotes systemic inflammation, vascular instability, and multi-organ failure. The Angiopoietin–TIE2 axis regulates endothelial function via Ang-1/Ang-2 balance, and elevated Ang-2 with a high Ang-2/1 ratio predicts poor outcomes in critical illness. This prospective study measured serum Ang-1, Ang-2, and Ang-2/1 ratio on postburn day 1 to evaluate endothelial dysfunction biomarkers and 30-day mortality prediction.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages10

Reading Time25 min

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Abstract

Introduction

ORIGINAL ARTICLE Early Dysregulation ofAngiopoietin-1 and-2 as a Predictor of Mortality in Critically Ill Burn Patients Ryan M. Johnson, MD1 , 2 , * ; Abigail Plum, MPH2 ; Kevin E. Galicia, MD1 , 2 ; Irena B. Helenowski, PhD2 ; Madison D. Kipp, BS2 ; Mary Grace Murray, BA2 ; Richard Gonzalez, MD1 , 2 ; Mashkoor A. Choudhry, PhD2 ; John C. Kubasiak, MD1 , 2 , * Abstract Shock-induced endothelial dysfunction plays a critical role in burn pathophysiology, with endothelial glycocalyx layer degradation promoting systemic inﬂammation, vascular instability, and multi-organ failure. The angiopoietin-tunica interna endothelial cell kinase (TIE2) axis, particularly the angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) balance, regulates endothelial function; elevated Ang-2 and a high Ang-2/1 ratio are linked to worse outcomes in critical illness. While well-documented in sepsis and trauma, effects of burn-induced angiopoietin dysregulation remain unclear. This study evaluates Ang-1, Ang-2, and the Ang-2/1 ratio as biomarkers of endothelial dysfunction and predictors of 30-day mortality in patients with burn injuries. In this prospective study, 62 adult patients with burn injuries were enrolled (January 2021–November 2024), with serum Ang-1 and Ang-2 measured via enzyme-linked immunosorbent assay on postburn day 1 . Of 62 patients, 52 were analyzed; 78.05% of survivors and 90.91% of non-survivors were male. Median age was 45 (survivors) vs 54 years (non-survivors, P = .139) . Non-survivors trended toward burns > 20% TBSA (72.73% vs 41.46%, P = .093). Ang-1 was lower in non-survivors (3.96 vs 7.97 ng/mL, P < .001), predicting early mortality (area under the receiver operating characteristic [AUROC]: 0.82) with a cut-off of 4.825 ng/mL and decreased mortality risk (odds ratio [OR]: 0.63, 95% conﬁdence interval [CI]: 0.40-0.87, P = .017). Ang-2 was higher (6.07 vs 1.99 ng/mL, P < .001; AUROC: 0.95), with a cut-off of 3.554 ng/mL. The Ang-2/1 ratio was elevated (1.59 vs 0.23, P < .001; AUROC: 0.93), with a cut-off of 0.504 and increased mortality risk (OR: 2.17, 95% CI: 1.10-5.12, P = .038) . Early Ang-1, Ang-2, and Ang-2/1 ratio levels correlate with 30-day mortality and may guide early prognostication. Key words: burn injury; endothelial glycocalyx; endotheliopathy; angiopoietin; prognostic biomarkers. INTRODUCTION Patients with severe burns (>20% of total body surface area [%TBSA]) undergo a profound and sustained immune 1 Department of Surgery, Loyola University Medical Center, Maywood, IL 60153, United States; 2 Burn and Shock Trauma Research Institute, Loyola University Chicago, Maywood, IL 60153, United States Author contributions: Ryan M. Johnson (Data curation [lead], Formal analysis [equal], Investigation [lead], Supervision [supporting], Validation [equal], Visualization, Writing—original draft, Writing—review & editing [lead]), Abigail Plum (Data curation, Investigation [equal], Validation, Writing—review & editing [supporting]), Kevin E. Galicia (Data curation [supporting], Investigation [equal], Validation, Writing—review & editing [supporting]), Irena B. Helenowski (Data curation, Formal analysis [equal], Validation, Visualization, Writing—review & editing [supporting]), Madison D. Kipp (Data curation, Writing—original draft, Writing—review & editing [supporting]), Mary Grace Murray (Investigation, Validation, Writing—review & editing [supporting]), Richard Gonzalez (Validation, Writing—review & editing [supporting]), MashkoorA. Choudhry (Funding acquisition, Validation, Writing—review & editing [supporting]), and John C. Kubasiak (Conceptualization [lead], Data curation, Formal analysis [supporting], Funding acquisition, Investigation, Methodology, Project administration, Resources, Software, Supervision [lead], Validation [equal], Visualization, Writing—original draft, Writing—review & editing [supporting]) Funding: This work is supported by the National Institute of General Medical Sciences (

FAQs

What was the main aim of this study?

To evaluate Ang-1, Ang-2, and the Ang-2/1 ratio as biomarkers of endothelial dysfunction and as predictors of 30-day mortality in critically ill burn patients.

How were Angiopoietin levels measured and when were samples collected?

Serum Ang-1 and Ang-2 were measured via enzyme-linked immunosorbent assay on postburn day 1.

Which angiopoietin-related measures were associated with 30-day mortality?

Non-survivors had lower Ang-1, higher Ang-2, and an elevated Ang-2/1 ratio, and these early levels correlated with 30-day mortality and prognostication.

Sep 29, 2026

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