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Author Spotlight: Developing Innovative Therapeutic Strategies for Hemorrhagic Shock Research
Published on: March 22, 2024
Biomarkers of endothelial cell dysfunction persist beyond resuscitation in patients with hemorrhagic shock
Ahmad Zeineddin1, Feng Wu, Wei Chao
1From the Department of Surgery (A.Z.), Shock Trauma and Anesthesiology Research Organized Research Center, Baltimore, Maryland; Shock Trauma and Anesthesiology Research Organized Research Center (A.Z., F.W., W.C., L.Z., R.V., H.H., R.A.K.), Department of Anesthesia (W.C., L.Z., H.H.), and Department of Surgery (A.M.C.), University of Maryland School of Medicine, Baltimore, Maryland; Bloodworks Research Institute (J.F.D.); Hematology Division, Department of Medicine (J.F.D.), University of Washington School of Medicine, Seattle, Washington; Department of Laboratory Medicine (S.P.), Department of Surgery, University of California, San Francisco, San Francisco, California; and Shock Trauma Center (R.A.K.), University of Maryland School of Medicine, Baltimore, Maryland.
Background:
It has been shown that microRNA-19b (miR-19b) binds to and degrades syndecan-1 after hemorrhagic shock (HS) and contributes to endothelial dysfunction in vitro and in vivo. The objective of the current study was to assess longitudinal changes in miR-19b and syndecan-1 in HS patients.
Methods:
Blood samples from HS patients (blood pressure <90 mm Hg and ≥2 U blood) were collected upon admission, completion of hemostasis, and after 24 hours for miR-19b (quantitative reverse transcription PCR) and syndecan-1 (enzyme-linked immunosorbent assay) and compared with controls and minimally injured (Injury Severity Score, ≤9). Inflammatory cytokines were measured (Luminex [Thermo Fisher, Waltham, MA]). Correlations between syndecan-1, miR-19b, inflammatory markers, and patient outcomes were performed. Logistic regression models were developed for outcomes.
Results:
Thirty-four HS patients were studied: age, 46 (19-89) years; male, 82%; penetrating, 35%; Injury Severity Score, 24 ± 10; and blood products at 24 hours, 21 ± 19 U. MicroRNA-19b was increased upon arrival and further increased over time: 4.6 → 6.7 → 24.1-fold change compared with 0.1 and 1.2 for minimally injured patients and controls, respectively. Syndecan-1 was increased to 42.6 → 50 → 51.5 ng/mL over time compared with 14.7 and 23.5 for minimally injured and controls, respectively. Values for both biomarkers remained significantly increased through 24 hours and were associated with a persistent increase in inflammatory cytokines. Admission syndecan-1 significantly predicted mortality, coagulopathy, and massive transfusion.
Conclusion:
We have shown for the first time that miR-19b and syndecan-1 were biomarkers for endothelial dysfunction independent of resuscitation. MicroRNA-19b did not demonstrate a strong correlation with syndecan-1 nor outcomes. Admission syndecan-1, however, remains a strong prognostic marker, but its elevation over time suggests a versatile role following HS that requires further investigation.
Level Of Evidence:
Prognostic/Epidemiological; Level II.
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