scholarly journals ICU Admission Levels of Endothelial Biomarkers as Predictors of Mortality in Critically Ill COVID-19 Patients

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 186
Author(s):  
Alice G. Vassiliou ◽  
Chrysi Keskinidou ◽  
Edison Jahaj ◽  
Parisis Gallos ◽  
Ioanna Dimopoulou ◽  
...  
Keyword(s):  
Critically Ill ◽  
Roc Curves ◽  
Endothelial Damage ◽  
Intercellular Adhesion Molecule ◽  
Vascular Endothelial ◽  
Intercellular Adhesion Molecule 1 ◽  
Icu Admission ◽  
Kaplan Meier ◽  
Mortality Probability ◽  
Von Willebrand

Endotheliopathy is suggested to be an important feature of COVID-19 in hospitalized patients. To determine whether endotheliopathy is involved in COVID-19-associated mortality, markers of endothelial damage were assessed in critically ill COVID-19 patients upon intensive care unit (ICU) admission. Thirty-eight critically ill COVID-19 patients were included in this observational study, 10 of whom died in the ICU. Endothelial biomarkers, including soluble (s)E-selectin, sP-selectin, angiopoietin 1 and 2 (Ang-1 and Ang-2, respectively), soluble intercellular adhesion molecule 1 (sICAM-1), vascular endothelial growth factor (VEGF), soluble vascular endothelial (VE)-cadherin, and von Willebrand factor (vWf), were measured upon ICU admission. The ICU cohort was subsequently divided into survivors and non-survivors; Kaplan–Meier analysis was used to explore associations between biomarkers and survival, while receiver operating characteristic (ROC) curves were generated to determine their potential prognostic value. sE-selectin, sP-selectin, Ang-2, and sICAM-1 were significantly elevated in ICU non-survivors compared to survivors, and also associated with a higher mortality probability in the Kaplan–Meier analysis. The prognostic values of sE-selectin, Ang-2, and sICAM-1 from the generated ROC curves were greater than 0.85. Hence, we conclude that in our cohort, ICU non-survivors had higher levels of specific endothelial markers compared to survivors. Elevated levels of these markers upon ICU admission could possibly predict mortality in COVID-19.

Prediction of VOD Using Biomarkers of Endothelial Injury.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3267-3267
Author(s):  
Corey Cutler ◽  
J. Aldridge ◽  
H. T. Kim ◽  
S. Ayanian ◽  
G. Bradwin ◽  
...  
Keyword(s):  
Conditioning Regimen ◽  
Elevated Serum ◽  
Endothelial Damage ◽  
Endothelial Injury ◽  
Intercellular Adhesion Molecule ◽  
P Value ◽  
Intercellular Adhesion Molecule 1 ◽  
Wilcoxon Rank Sum Test ◽  
Gvhd Prophylaxis ◽  
Von Willebrand

Abstract Veno-occlusive disease (VOD) of the liver occurs with a frequency of 5–15% after myeloablative conditioning and allogeneic stem cell transplantation (SCT). While risk factors for VOD are well known, predicting the occurrence of VOD in individuals remains challenging. Since the primary mechanism of injury in VOD is conditioning-related damage to hepatic sinusoidal endothelial cells and hepatocytes, we measured soluble biomarkers of endothelial injury in the peri-transplant period to determine if they correlated with the occurrence of VOD. Methods: 59 patients received cyclophosphamide (1800 mg/m2 x 2) and TBI (14 Gy) as conditioning therapy, and tacrolimus with sirolimus (Sir+) or methotrexate (Sir-) as GVHD prophylaxis. Only patients with HLA-matched donors were included and selected for analysis based on the occurrence of VOD (VOD+ n=18, VOD- n=41), diagnosed by clinical, radiologic and pathologic criteria. Banked samples collected after conditioning but prior to SCT (day -1) and weekly after SCT (day 7, 14, 21) were thawed and analyzed by ELISA using commercially available kits and quantified using a VersaMax plate reader. Von Willebrand Factor (vWF) and thrombomodulin were assayed in plasma, and E-selectin and soluble intercellular adhesion molecule-1 (ICAM) were assayed in serum. Assays were performed in duplicate and results are the mean of two assays. Not all patients had every time point analyzed due to missing specimens. The within-sample results were compared using the 2-sided Wilcoxon rank-sum test, and the Bonferroni method was used to adjust for multiple comparisons (p value for significance=0.0125). Results: Comparing patients who did and did not develop VOD, patients with VOD had significantly elevated levels of vWF suggestive of endothelial damage at all timepoints prior to the development of VOD in comparison with controls (p≤0.0118, Figure). Thrombomodulin levels were predictive of VOD at all post-SCT timepoints (p≤0.0013, Figure). ICAM levels were significantly elevated up to Day 21 (p≤0.0028). E-selectin was less useful and statistically significant increases in levels were not observed. Since sirolimus has effects on endothelial function that may contribute to VOD through mechanisms different than the conditioning regimen, we stratified the analyses by sirolimus exposure, comparing Sir+VOD+ patients with Sir+VOD- controls. vWF levels in Sir+VOD+ patients were predictive for VOD at all timepoints when compared with controls (p≤0.003). Thrombomodulin levels were informative against controls for all post-SCT timepoints (p≤0.003). ICAM was informative as well (p≤0.003 pre-SCT, day 7, 14), while E-selectin levels were uninformative. The discriminative value of elevated serum and plasma biomarkers was limited to Sir+ patients in this small dataset, since other than some vWF timepoints, biomarkers could not distinguish Sir- patients who developed VOD patients from control groups without VOD. There were no differences in biomarkers among VOD- patients, suggesting that in the absence of VOD, markers of endothelial injury are not elevated even when sirolimus is used. Conclusions: Plasma vWF and thrombomodulin and serum ICAM elevations before and early after SCT can be used to predict the occurrence of VOD. These assays are most useful in patients receiving sirolimus. This analysis demonstrates the contribution of sirolimus to endothelial injury and VOD after SCT, and may help select patients in whom prophylactic or pre-emptive strategies against endothelial damage and VOD may be useful. Figure Figure

scholarly journals Endothelial, Immunothrombotic, and Inflammatory Biomarkers in the Risk of Mortality in Critically Ill COVID-19 Patients: The Role of Dexamethasone

Diagnostics ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1249
Author(s):  
Chrysi Keskinidou ◽  
Alice G. Vassiliou ◽  
Alexandros Zacharis ◽  
Edison Jahaj ◽  
Parisis Gallos ◽  
...  
Keyword(s):  
Critically Ill ◽  
Mortality Risk ◽  
Roc Curves ◽  
Mortality Prediction ◽  
Prognostic Biomarkers ◽  
Inflammatory Biomarkers ◽  
Rank Test ◽  
Icu Mortality ◽  
Icu Admission ◽  
Kaplan Meier

Endothelial dysfunction, coagulation and inflammation biomarkers are increasingly emerging as prognostic markers of poor outcomes and mortality in severe and critical COVID-19. However, the effect of dexamethasone has not been investigated on these biomarkers. Hence, we studied potential prognostic biomarkers of mortality in critically ill COVID-19 patients who had either received or not dexamethasone. Biomarker serum levels were measured on intensive care unit (ICU) admission (within 24 h) in 37 dexamethasone-free and 29 COVID-19 patients who had received the first dose (6 mg) of dexamethasone. Receiver operating characteristic (ROC) curves were generated to assess their value in ICU mortality prediction, while Kaplan–Meier analysis was used to explore associations between biomarkers and survival. In the dexamethasone-free COVID-19 ICU patients, non-survivors had considerably higher levels of various endothelial, immunothrombotic and inflammatory biomarkers. In the cohort who had received one dexamethasone dose, non-survivors had higher ICU admission levels of only soluble (s) vascular cell adhesion molecule-1 (VCAM-1), soluble urokinase-type plasminogen activator receptor (suPAR) and presepsin. As determined from the generated ROC curves, sVCAM-1, suPAR and presepsin could still be reliable prognostic ICU mortality biomarkers, following dexamethasone administration (0.7 < AUC < 0.9). Moreover, the Kaplan–Meier survival analysis showed that patients with higher than the median values for sVCAM-1 or suPAR exhibited a greater mortality risk than patients with lower values (Log-Rank test, p < 0.01). In our single-center study, sVCAM-1, suPAR and presepsin appear to be valuable prognostic biomarkers in assessing ICU mortality risk in COVID-19 patients, even following dexamethasone administration.

IL6 rs1800795 SNP may relate to cardiovascular pathology in alcohol abusers

2021 ◽  
pp. 30-42
Author(s):  
Д.И. Перегуд ◽  
В.Ю. Баронец ◽  
А.С. Лобачева ◽  
А.С. Иванов ◽  
И.В. Гармаш ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Clinical Manifestations ◽  
Serum Levels ◽  
Intercellular Adhesion Molecule ◽  
Vascular Endothelial ◽  
Intercellular Adhesion Molecule 1 ◽  
Alcohol Abusers ◽  
Cardiovascular Pathology ◽  
Genetically Determined ◽  
Endothelial Growth Factor

Формирование сердечно-сосудистой патологии при чрезмерном употреблении алкоголя сопряжено с повышением концентрации в крови таких медиаторов воспаления, как интерлейкины 6 (IL6) и 8 (IL8) и хемоаттрактанта моноцитов CCL2 (C-C motif ligand 2), а также молекул, участвующих в функционировании эндотелия, в частности фактора роста сосудистого эндотелия (VEGFA, vascular endothelial growth factor А), молекулы клеточной адгезии (ICAM1, intercellular adhesion molecule 1) и эндотелина (EDN1). Предполагается, что данный процесс генетически детерминирован, однако до настоящего момента исследований в этом направлении не проводилось. Целью работы явилось изучение ассоциации носительства аллелей полиморфных локусов, расположенных в генах IL6 (rs1800795), IL8 (rs4073), CCL2 (rs1024611), VEGFA (rs699947 и rs2010963), ICAM1 (rs281437) и EDN1 (rs1800541) с содержанием соответствующих полипептидов в циркуляторном русле и развитием сердечно-сосудистых заболеваний на фоне хронического злоупотребления алкоголем. В исследование были включены лица, злоупотребляющие алкоголем, без выраженной соматической патологии, а также пациенты, у которых на фоне злоупотребления развились заболевания сердечно-сосудистой системы. Уровень IL6, IL8, CCL2, VEGFA, ICAM1 и EDN1 в сыворотке крови оценивали посредством ИФА. Аллели полиморфных локусов были определены посредством ПЦР в режиме реального времени. Установлено, что среди лиц, злоупотребляющих алкоголем, с клинически выраженной патологией сердечно-сосудистой системы значительно чаще встречаются только носители гомозиготного генотипа GG или аллеля G полиморфного локуса в гене IL6 (rs1800795). Кроме того, носительство генотипа GG повышает вероятность развития сердечно-сосудистых заболеваний при хроническом злоупотреблении алкоголем. Однако, дополнительное влияние оказывают демографические факторы и клинические характеристики пациентов. В частности, введение поправки на возраст и пол, а также учет наличия цирроза печени, гипертензии и сахарного диабета, сопровождающих злоупотребление алкоголем, нивелируют повышение риска патологии сердечно-сосудистой системы. Ассоциации полиморфных вариантов в генах IL6 (rs1800795), IL8 (rs4073), CCL2 (rs1024611), VEGFA (rs699947 и rs2010963), ICAM1 (rs281437) и EDN1 (rs1800541) с содержанием белковых продуктов соответствующих генов в циркуляторном русле выявлено не было. Cardiovascular diseases in alcohol abusers are associated with elevation of plasma levels of proinflammatory cytokines such as IL6, IL8 and CCL2 as well as molecules involved in endothelial functioning including VEGFA, ICAM1 and EDN1. This phenomenon is supposed to be genetically determined. However to date the issue has not been investigated. Thus, we aimed to study the relationship between carriage of SNPs of IL6 (rs1800795), IL8 (rs4073), CCL2 (rs1024611), VEGFA (rs699947 and rs2010963), ICAM1 (rs281437) and EDN1 (rs1800541) genes with the serum levels of their products and the development of cardiovascular diseases in alcohol abusers. The study included alcohol abusers without apparent somatic pathology and alcohol abusers with clinical manifestations of cardiovascular disease. Serum levels of IL6, IL8, CCL2, VEGFA, ICAM1 and EDN1 were estimated by EIA. SNPs were determined by means of real-time PCR. We found that among the SNPs studied only carriers of homozygous GG genotype and G allele of IL6 (rs1800795) were more frequent in alcohol abusers with cardiovascular diseases. Moreover, carriage of homozygous GG genotype of IL6 (rs1800795) increases the probability of development of cardiovascular pathology in alcohol abusers. However, adjustment for age, gender and the presence of liver cirrhosis, hypertension and diabetes mellitus as co-variates eliminates the enhanced risk of cardiovascular pathology. Polymorphisms of IL6 (rs1800795), IL8 (rs4073), CCL2 (rs1024611), VEGFA (rs699947 and rs2010963), ICAM1 (rs281437) and EDN1 (rs1800541) did not determine serum levels of the related polypeptides.

scholarly journals Antioxidant and Anti-Inflammatory Effects of Blueberry Anthocyanins on High Glucose-Induced Human Retinal Capillary Endothelial Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Wuyang Huang ◽  
Zheng Yan ◽  
Dajing Li ◽  
Yanhong Ma ◽  
Jianzhong Zhou ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
High Glucose ◽  
Vascular Endothelial Cell ◽  
Intercellular Adhesion Molecule ◽  
Vascular Endothelial ◽  
Intercellular Adhesion Molecule 1 ◽  
Eye Health ◽  
Retinal Capillary ◽  
Capillary Endothelial Cells ◽  
Anti Inflammatory

Blueberries possess abundant anthocyanins, which benefit eye health. The purpose of this study was to explore the protective functional role of blueberry anthocyanin extract (BAE) and its predominant constituents, malvidin (Mv), malvidin-3-glucoside (Mv-3-glc), and malvidin-3-galactoside (Mv-3-gal), on high glucose- (HG-) induced injury in human retinal capillary endothelial cells (HRCECs). The results showed that BAE, Mv, Mv-3-glc, and Mv-3-gal enhanced cell viability (P<0.05 versus the HG group at 24 h); decreased the reactive oxygen species (ROS, P<0.01 versus the HG group both at 24 and 48 h); and increased the enzyme activity of catalase (CAT) and superoxide dismutase (SOD) (P<0.05 versus the HG group both at 24 and 48 h). Mv could greatly inhibit HG-induced Nox4 expression both at 24 and 48 h (P<0.05), while BAE and Mv-3-gal downregulated Nox4 only at 48 h (P<0.05). Mv, Mv-3-glc, and Mv-3-gal also changed nitric oxide (NO) levels (P<0.05). BAE and Mv-3-glc also influenced angiogenesis by decreasing the vascular endothelial cell growth factor (VEGF) level and inhibiting Akt pathway (P<0.05). Moreover, Mv and Mv-3-glc inhibited HG-induced intercellular adhesion molecule-1 (ICAM-1, P<0.001) and nuclear factor-kappa B (NF-κB) (P<0.05). It indicated that blueberry anthocyanins protected HRCECs via antioxidant and anti-inflammatory mechanisms, which could be promising molecules for the development of nutraceuticals to prevent diabetic retinopathy.

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