Lipidomic and proteomic characterization of platelet extracellular vesicle subfractions from senescent platelets

Pienimaeki‐Roemer, Annika; Kuhlmann, Katja; Böttcher, Alfred; Konovalova, Tatiana; Black, A. Kobza; Orsó, Evelyn; Liebisch, Gerhard; Ahrens, Maike; Eisenacher, Martin; Meyer, Helmut E.; Schmitz, Gerd

doi:10.1111/trf.12874

Cited by 105 publications

(92 citation statements)

References 88 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Platelet microparticle release is a marker for platelet activation and increases with storage time in platelet products . We found no significant differences between 7‐day RT‐stored and 5‐day, 4°C–stored platelets (Fig.…”

Section: Resultsmentioning

confidence: 69%

Effects of storage time prolongation on in vivo and in vitro characteristics of 4°C–stored platelets

et al. 2020

View full text Add to dashboard Cite

BACKGROUND Cold (4°C)‐stored platelets are currently under investigation for transfusion in bleeding patients. It is currently unknown how long cold‐stored platelets can be stored for clinical applications. STUDY DESIGN AND METHODS Twenty three subjects were recruited. Twenty‐one subjects were available for in vivo assessment and received indium‐111 radiolabeled, cold‐stored platelets. We investigated 5‐ (n = 5), 10‐ (n = 6), 15‐ (n = 5), and 20‐day–stored (n = 5) platelets and obtained samples for in vitro testing at baseline and after the designated storage time. Twenty three units were available for in vitro testing. Five‐ and 7‐day (n = 5 each), room temperature (RT)‐stored platelets served as the current clinical standard control. RESULTS In vivo, we found a continuous decline in platelet recovery from 5 to 20 days. Platelet survival reached a low nadir after 10 days of storage. Ex vivo, we observed the maximum platelet αIIbβ3 integrin response to collagen at 5 days of cold storage, and we saw a continuous decline thereafter. However, platelet integrin activation and mitochondrial membrane integrity were better preserved after 20 days at 4°C, compared to 5 days at RT. Platelet metabolic parameters suggest comparable results between 20‐day cold‐stored platelets and 5‐ or 7‐day RT‐stored platelets. CONCLUSION In summary, we performed the first studies with extended, cold‐stored, apheresis platelets in plasma for up to 20 days with a fresh comparator. Storing cold‐stored platelets up to 20 days yields better results in vitro, but further studies in actively bleeding patients are needed to determine the best compromise between hemostatic efficacy and storage prolongation.

show abstract

Section: Resultsmentioning

confidence: 69%

Effects of storage time prolongation on in vivo and in vitro characteristics of 4°C–stored platelets

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Nomenclature of these subpopulations is nonstandard; however, according the International Society for Extracellular Vesicles, small EVs consist of cell populations <100 or <200 nmol/L in size and are often referred to as exosomes . Small PEVs are known to carry numerous thrombotic mediators . To investigate if there were differential effects of the EV subpopulations released following trauma, small PEVs were isolated from mice subjected to polytrauma and used in adoptive transfer into mice for DVT analysis.…”

Section: Resultsmentioning

confidence: 99%

“…As demonstrated in (D), labeled PEV (red) localize to the thrombus site and interact with platelets (green) suggesting PEVs have direct role in regulating thrombus development are known to carry numerous thrombotic mediators. [39][40][41] To investigate if there were differential effects of the EV subpopulations released following trauma, small PEVs were isolated from mice subjected to polytrauma and used in adoptive transfer into mice for DVT analysis. To confirm we were working with small PEVs, we characterized the isolated subpopulation by size exclusion chromatography, nanoparticle tracking analysis, and western blot analysis for the surface marker CD9 ( Figure S3).…”

Section: Trauma-derived Pevs and Small Pevs Containing Exosomes Enhmentioning

confidence: 99%

Platelet‐derived extracellular vesicles released after trauma promote hemostasis and contribute to DVT in mice

Dyer

Alexander

Hassoune

et al. 2019

Journal of Thrombosis and Haemostasis

View full text Add to dashboard Cite

Background Traumatic injury can lead to dysregulation of the normal clotting system, resulting in hemorrhagic and thrombotic complications. Platelet activation is robust following traumatic injury and one process of platelet activation is to release of extracellular vesicles (PEV) that carry heterogenous cargo loads and surface ligands. Objectives We sought to investigate and characterize the release and function of PEVs generated following traumatic injury. Methods PEV content and quantity in circulation following trauma in humans and mice was measured using flow cytometry, size exclusion chromatography, and nanoparticle tracking analysis. PEVs were isolated from circulation and the effects on thrombin generation, bleeding time, hemorrhage control, and thrombus formation were determined. Finally, the effect of hydroxychloroquine (HCQ) on PEV release and thrombosis were examined. Results Human and murine trauma results in a significant release of PEVs into circulation compared with healthy controls. These PEVs result in abundant thrombin generation, increased platelet aggregation, decreased bleeding times, and decreased hemorrhage in uncontrolled bleeding. Conversely, PEVs contributed to enhanced venous thrombus formation and were recruited to the developing thrombus site. Interestingly, HCQ treatment resulted in decreased platelet aggregation, decreased PEV release, and reduced deep vein thrombosis burden in mice. Conclusions These data demonstrate that trauma results in significant release of PEVs which are both pro‐hemostatic and pro‐thrombotic. The effects of PEVs can be mitigated by treatment with HCQ, suggesting the potential use as a form of deep vein thrombosis prophylaxis.

show abstract

“…The cargoes contained within EVs reflect both the intracellular origin of the cargo as well as the cell type from which the vesicle was derived. We refer readers to the many profiling studies which have been published on this subject for further information . Prototypical exosome markers include tetraspannins such as CD9, CD63 and CD81, and ESCRT proteins Alix and TSG101 .…”

Section: Functional Cargoes In Microvesicles Derived From Tumor Cellsmentioning

confidence: 99%

The biology of extracellular microvesicles

Sedgwick

D’Souza‐Schorey

2018

Traffic

192

162

View full text Add to dashboard Cite

The study of extracellular vesicles (EVs) is a rapidly evolving field, owing in large part to recent advances in the realization of their significant contributions to normal physiology and disease. Once discredited as cell debris, these membrane vesicles have now emerged as mediators of intercellular communication by interaction with target cells, drug and gene delivery, and as potentially versatile platforms of clinical biomarkers as a result of their distinctive protein, nucleic acid and lipid cargoes. While there are multiple classes of EVs released from almost all cell types, here we focus primarily on the biogenesis, fate and functional cargoes of microvesicles (MVs). MVs regulate many important cellular processes including facilitating cell invasion, cell growth, evasion of immune response, stimulating angiogenesis, drug resistance and many others.

show abstract

Lipidomic and proteomic characterization of platelet extracellular vesicle subfractions from senescent platelets

Cited by 105 publications

References 88 publications

Effects of storage time prolongation on in vivo and in vitro characteristics of 4°C–stored platelets

Effects of storage time prolongation on in vivo and in vitro characteristics of 4°C–stored platelets

Platelet‐derived extracellular vesicles released after trauma promote hemostasis and contribute to DVT in mice

The biology of extracellular microvesicles

Contact Info

Product

Resources

About