Flow analysis of individual blood extracellular vesicles in acute coronary syndrome

Vagida, Murad; Arakelyan, Anush; Lebedeva, A.; Grivel, Jean‐Charles; Shpektor, A.; Vasilieva, Elena; Margolis, Leonid

doi:10.1080/09537104.2016.1212002

Cited by 14 publications

(11 citation statements)

References 57 publications

(63 reference statements)

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“…Interest in EVs as an immune mechanism has increased with the evolving ability to measure these sub‐cellular particles, and it is now possible to determine the cell of origin of EVs by staining for cell surface markers . It is known that the content of EVs in RBC units changes with blood storage .…”

Section: Discussionmentioning

confidence: 99%

“…Interest in EVs as an immune mechanism has increased with the evolving ability to measure these sub-cellular particles, and it is now possible to determine the cell of origin of EVs by staining for cell surface markers. 18,19 It is known that the content of EVs in RBC units changes with blood storage. [19][20][21][22] We hypothesized that it would be unlikely that RBC unit-derived EVs would be detectable in the circulation of transfusion recipients, both due to dilution in the recipient and data from mouse models showing that these particles are rapidly cleared by the reticuloendothelial system.…”

Section: Discussionmentioning

confidence: 99%

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Influence of blood storage age on immune and coagulation parameters in critically ill transfused patients

et al. 2019

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BACKGROUND Several retrospective studies have suggested that transfusion with red blood cells (RBCs) stored for longer periods is associated with increased mortality. The Age of Blood Evaluation (ABLE) study randomized subjects to receive fresh vs. standard issue RBC units and showed no difference in the primary or secondary endpoints of mortality or change in multi‐organ dysfunction syndrome (MODS) score. METHODS In this study a subset of 100 ABLE subjects were enrolled to measure coagulation and immune parameters. Samples were collected pre‐transfusion and on days 2, 6, 28, and 180 post‐transfusion. Levels of 16 coagulation parameters, regulatory and functional T cells, 25 cytokines, and 16 markers of extracellular vesicles (EVs) were determined. RESULTS Changes from baseline in levels of protein C, factor V, and EVs expressing phosphatidyl serine and CTLA‐4 (CD152) differed between recipients of fresh and standard storage age RBC units, with the vast majority of coagulation and EV markers and all cytokines tested showing no difference between study arms. Although most analytes showed no difference between subjects in the fresh and standard arms of the study, 6 coagulation parameters, 15 cytokines, and 7 EV parameters changed significantly in the period post‐transfusion. DISCUSSION Transfusion of fresh vs. standard issue RBC units does not result in substantial changes in coagulation or immune parameters, up to day 35 of RBC storage. Furthermore, significant changes in multiple coagulation and immune parameters are detectable post‐transfusion, though causality cannot be determined based on the current study.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Influence of blood storage age on immune and coagulation parameters in critically ill transfused patients

et al. 2019

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“…Various surface markers of EVs have been identified. Antibodies to CD9, CD63, CD81, and MHC class 1 (MHC1) have been used for immunoaffinity purification of EVs bearing these membrane proteins 16 – 18 , but the efficiency of these capture methods is not well documented and requires optimization of the ratio of magnetic particles versus EVs. Furthermore, it is unclear whether EVs produced by the same cell but lacking these markers differ in their RNA content or functional activity.…”

Section: Introductionmentioning

confidence: 99%

CD63, MHC class 1, and CD47 identify subsets of extracellular vesicles containing distinct populations of noncoding RNAs

Kaur

Elkahloun

Arakelyan

et al. 2018

Sci Rep

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Extracellular vesicles (EVs) mediate the intercellular transfer of RNAs, which alter gene expression in target cells. EV heterogeneity has limited progress towards defining their physiological functions and utility as disease-specific biomarkers. CD63 and MHC1 are widely used as markers to purify EVs. CD47 is also present on EVs and alters their effects on target cells, suggesting that specific surface markers define functionally distinct EVs. This hypothesis was addressed by comparing Jurkat T cell EVs captured using CD47, CD63, and MHC1 antibodies. These EV subsets have similar sizes but divergent RNA contents. Apart from differences in numbers of nonannotated transcripts, CD63+, MHC1+, and CD47+ EVs have similar overall contents of most noncoding RNA classes, but the relative enrichment of specific RNAs differs. The enrichment of micro-RNAs is highly divergent, and some including miR320a are selectively concentrated in CD47+ EVs. Small nucleolar RNAs including SNORD116@ and SNHG10 are also selectively enriched in CD47+ EVs, whereas no small nuclear RNAs are enriched in CD47+ EVs. Conversely, MHC1+ EVs are selectively enriched in a subset of tRNAs including TRE-CTC and TRR-CCG. This heterogeneity in RNA composition suggests multiple sorting mechanisms that direct specific RNAs into subsets of EVs that express specific surface markers.

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“…Recently, it was found immune activation is associated with the release by activated cells of nanosized EV that mediate cellcell communication and play an important role in immune activation (30)(31). In cardiovascular diseases, EV are released predominantly by activated platelets (14)(15)(16)(32)(33). Activation of platelets as well as of monocytes results in an increase in their adhesion to various surfaces as well as aggregation with other cells, in particular with monocytes, forming MPC in blood (34).…”

Section: Discussionmentioning

confidence: 99%

Monocytes of Different Subsets in Complexes with Platelets in Patients with Myocardial Infarction

et al. 2018

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Acute myocardial infarction (AMI) is associated with activation of various cells, including platelets that form monocyte–platelet complexes (MPCs). Here, we analysed MPC in vivo and in vitro and investigated the abilities of different monocyte subclasses to form MPC, the characteristics of the cells involved in MPC formation and MPC changes in AMI. We identified MPC by co-staining for platelet antigen CD41a and monocyte antigens CD14 and CD16. Platelet activation was evaluated from expression of phosphatidylserine as revealed by annexin V. Our results confirm published data and provide new information regarding the patterns of MPC in AMI patients. We found that the patterns of platelet aggregation with monocytes were different in AMI patients and controls: (1) in AMI patients, MPC formed by intermediate monocytes carry more platelets whereas in healthy controls more platelets aggregated with classical monocytes; (2) the numbers of MPC in AMI patients, being already higher than in controls, were further increased if these patients suffered various in-hospital complications; (3) on the basis of the CD41a fluorescence of the antibody-stained MPC, some of the aggregates seem to consist of monocytes and platelet-derived extracellular vesicles (EVs); (4) aggregation of monocytes with platelet EV occurred in in vitro experiments; and (5) these experiments demonstrated that monocytes from AMI patients aggregate with both platelets and platelet EVs more efficiently than do monocytes from controls. MPC in AMI patients may play an important role in this pathology.

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Flow analysis of individual blood extracellular vesicles in acute coronary syndrome

Cited by 14 publications

References 57 publications

Influence of blood storage age on immune and coagulation parameters in critically ill transfused patients

Influence of blood storage age on immune and coagulation parameters in critically ill transfused patients

CD63, MHC class 1, and CD47 identify subsets of extracellular vesicles containing distinct populations of noncoding RNAs

Monocytes of Different Subsets in Complexes with Platelets in Patients with Myocardial Infarction

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