Microvesicle Formation Induced by Oxidative Stress in Human Erythrocytes

Sudnitsyna, Julia; Skverchinskaya, Elisaveta; Dobrylko, Irina; Никитина, Е. Р.; Gambaryan, Stepan; Mindukshev, Igor

doi:10.3390/antiox9100929

Cited by 52 publications

(41 citation statements)

References 68 publications

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“…Since hemoglobin (Hb) is the main cytosolic protein of RBCs, it is one of the most prevalent molecules found in RBC-derived EVs ( Thangaraju et al, 2020 ) and it has been suggested that defects in Hb might be one of the primary triggers for vesiculation ( Leal et al, 2018 ). This is supported by the elimination of hemichromes or the redox active ferryl Hb ( Welbourn et al, 2017 ) via microvesicles in the case of thalassemic patients ( Ferru et al, 2014 ), or oxidatively challenged RBCs ( Sudnitsyna et al, 2020 ), respectively.…”

Section: Introductionmentioning

confidence: 99%

Deciphering the Relationship Between Free and Vesicular Hemoglobin in Stored Red Blood Cell Units

et al. 2022

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Red blood cells (RBCs) release hemoglobin (Hb)-containing extracellular vesicles (EVs) throughout their lifespan in the circulation, and especially during senescence, by spleen-facilitated vesiculation of their membrane. During ex vivo aging under blood bank conditions, the RBCs lose Hb, both in soluble form and inside EVs that accumulate as a part of storage lesion in the supernatant of the unit. Spontaneous hemolysis and vesiculation are increasingly promoted by the storage duration, but little is known about any physiological linkage between them. In the present study, we measured the levels of total extracellular and EV-enclosed Hb (EV-Hb) in units of whole blood (n = 36) or packed RBCs stored in either CPDA-1 (n = 99) or in CPD-SAGM additive solution (n = 46), in early, middle, and late storage. The spectrophotometry data were subjected to statistical analysis to detect possible correlation(s) between storage hemolysis and EV-Hb, as well as the threshold (if any) that determines the area of this dynamic association. It seems that the percentage of EV-Hb is negatively associated with hemolysis levels from middle storage onward by showing low to moderate correlation profiles in all strategies under investigation. Moreover, 0.17% storage hemolysis was determined as the potential cut-off, above which this inverse correlation is evident in non-leukoreduced CPDA units. Notably, RBC units with hemolysis levels > 0.17% are characterized by higher percentage of nanovesicles (<100 nm) over typical microvesicles (100–400 nm) compared with the lower hemolysis counterparts. Our results suggest an ordered loss of Hb during RBC accelerated aging that might fuel targeted research to elucidate its mechanistic basis.

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Section: Introductionmentioning

confidence: 99%

Deciphering the Relationship Between Free and Vesicular Hemoglobin in Stored Red Blood Cell Units

et al. 2022

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“…It is of interest that similar connections were detected with the ROS + PLTs pre-dialysis but not following it, probably due to the selective beneficial effect of HD on PLT (but not on RBC) ROS burden. Apart from these, RBCs subjected to oxidative stress could also contribute to the procoagulant status of ESRD patients through the release of PS + microvesicles [ 58 , 59 ]. The significantly increased fibrinogen observed post-HD in ESRD patients might further interact with RBCs promoting RBC-RBC and RBC-PLT aggregates [ 60 , 61 ].…”

Section: Discussionmentioning

confidence: 99%

Coagulation Abnormalities in Renal Pathology of Chronic Kidney Disease: The Interplay between Blood Cells and Soluble Factors

et al. 2021

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Coagulation abnormalities in renal pathology are associated with a high thrombotic and hemorrhagic risk. This study aims to investigate the hemostatic abnormalities that are related to the interaction between soluble coagulation factors and blood cells, and the effects of hemodialysis (HD) on it, in end stage renal disease (ESRD) patients. Thirty-two ESRD patients under HD treatment and fifteen healthy controls were included in the study. Whole blood samples from the healthy and ESRD subjects were collected before and after the HD session. Evaluation of coagulation included primary and secondary hemostasis screening tests, proteins of coagulation, fibrinolytic and inhibitory system, and ADAMTS-13 activity. Phosphatidylserine (PS) exposure and intracellular reactive oxygen species (iROS) levels were also examined in red blood cells and platelets, in addition to the platelet activation marker CD62P. Platelet function analysis showed pathological values in ESRD patients despite the increased levels of activation markers (PS, CD62P, iROS). Activities of most coagulation, fibrinolytic, and inhibitory system proteins were within the normal range, but HD triggered an increase in half of them. Additionally, the increased baseline levels of ADAMTS-13 inhibitor were further augmented by the dialysis session. Finally, pathological levels of PS and iROS were measured in red blood cells in close correlation with variations in several coagulation factors and platelet characteristics. This study provides evidence for a complex coagulation phenotype in ESRD. Signs of increased bleeding risk coexisted with prothrombotic features of soluble factors and blood cells in a general hyperfibrinolytic state. Hemodialysis seems to augment the prothrombotic potential, while the persisted platelet dysfunction might counteract the increased predisposition to thrombotic events post-dialysis. The interaction of red blood cells with platelets, the thrombus, the endothelium, the soluble components of the coagulation pathways, and the contribution of extracellular vesicles on hemostasis as well as the identification of the unknown origin ADAMTS-13 inhibitor deserve further investigation in uremia.

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“…Simulation of oxidative stress (OS) conditions was performed by incubation of (RBCs suspension 0.5 × 10 9 cell/mL with a widely used and well characterized oxidizing agent organic peroxide tert -Butyl hydroperoxide (tBuOOH, Sigma-Aldrich, Munich, Germany) in a Biosan-100 thermoshaker (BioSan, Latvia) for 4–5 h at 37 °C shaking at 420 rpm [ 32 , 33 , 34 , 35 , 36 ]. tBuOOH is an amphiphilic oxidizer, which causes complex damage both in the lipid layer of the membrane and in the cytosol of the cell.…”

Section: Methodsmentioning

confidence: 99%

Microfluidic Characterization of Red Blood Cells Microcirculation under Oxidative Stress

Besedina

Skverchinskaya

Ivanov

et al. 2021

Cells

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Microcirculation is one of the basic functional processes where the main gas exchange between red blood cells (RBCs) and surrounding tissues occurs. It is greatly influenced by the shape and deformability of RBCs, which can be affected by oxidative stress induced by different drugs and diseases leading to anemia. Here we investigated how in vitro microfluidic characterization of RBCs transit velocity in microcapillaries can indicate cells damage and its correlation with clinical hematological analysis. For this purpose, we compared an SU-8 mold with an Si-etched mold for fabrication of PDMS microfluidic devices and quantitatively figured out that oxidative stress induced by tert-Butyl hydroperoxide splits all RBCs into two subpopulations of normal and slow cells according to their transit velocity. Obtained results agree with the hematological analysis showing that such changes in RBCs velocities are due to violations of shape, volume, and increased heterogeneity of the cells. These data show that characterization of RBCs transport in microfluidic devices can directly reveal violations of microcirculation caused by oxidative stress. Therefore, it can be used for characterization of the ability of RBCs to move in microcapillaries, estimating possible side effects of cancer chemotherapy, and predicting the risk of anemia.

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Microvesicle Formation Induced by Oxidative Stress in Human Erythrocytes

Cited by 52 publications

References 68 publications

Deciphering the Relationship Between Free and Vesicular Hemoglobin in Stored Red Blood Cell Units

Deciphering the Relationship Between Free and Vesicular Hemoglobin in Stored Red Blood Cell Units

Coagulation Abnormalities in Renal Pathology of Chronic Kidney Disease: The Interplay between Blood Cells and Soluble Factors

Microfluidic Characterization of Red Blood Cells Microcirculation under Oxidative Stress

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