Ahmad Zeineddin1, Feng Wu1, Wei Chao, Lin Zhou, Roumen Vesselinov1, Amanda Chipman2, Jing Fei Dong, Huang Huang, Shibani Pati3, Rosemary A Kozar. 1. Shock Trauma and Anesthesiology Research Organized Research Center (STAR-ORC), University of Maryland School of Medicine, Baltimore, Maryland. 2. Department of Surgery, University of Maryland School of Medicine, Baltimore, MD US. 3. Department of Laboratory Medicine, Department of Surgery University of California San Francisco, San Francisco, CA US.
Abstract
BACKGROUND: It has been shown that microRNA-19b (miRNA-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 miRNA-19b and syndecan-1 in HS patients. METHODS: Blood samples from HS patients (blood pressure < 90 mmHg and ≥ 2 units blood) were collected upon admission, completion of hemostasis, and after 24 hours for miRNA-19b (RT-qPCR) and syndecan-1 (ELISA) and compared to controls and minimally injured (Injury severity score ISS ≤ 9). Inflammatory cytokines were measured (Luminex). Correlations between syndecan-1, miRNA-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), 82% male, 35% penetrating, ISS 24 ± 10, and blood products at 24 hours 21 ± 19 units. MiRNA-19b was increased upon arrival and further increased over time: 4.6 - > 6.7 - > 24.1 fold change compared to 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 to 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. CONCLUSIONS: We have shown for the first time that miR-19b and syndecan-1 were biomarkers for endothelial dysfunction independent of resuscitation. MiR-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 hemorrhagic shock that requires further investigation. LEVEL OF EVIDENCE: II - Prospective. STUDY TYPE: original research.
BACKGROUND: It has been shown that microRNA-19b (miRNA-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 miRNA-19b and syndecan-1 in HS patients. METHODS: Blood samples from HS patients (blood pressure < 90 mmHg and ≥ 2 units blood) were collected upon admission, completion of hemostasis, and after 24 hours for miRNA-19b (RT-qPCR) and syndecan-1 (ELISA) and compared to controls and minimally injured (Injury severity score ISS ≤ 9). Inflammatory cytokines were measured (Luminex). Correlations between syndecan-1, miRNA-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), 82% male, 35% penetrating, ISS 24 ± 10, and blood products at 24 hours 21 ± 19 units. MiRNA-19b was increased upon arrival and further increased over time: 4.6 - > 6.7 - > 24.1 fold change compared to 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 to 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. CONCLUSIONS: We have shown for the first time that miR-19b and syndecan-1 were biomarkers for endothelial dysfunction independent of resuscitation. MiR-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 hemorrhagic shock that requires further investigation. LEVEL OF EVIDENCE: II - Prospective. STUDY TYPE: original research.