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

被引：98

作者：

Pienimaeki-Roemer, Annika ^{[1
]}

Kuhlmann, Katja ^{[2
]}

Boettcher, Alfred ^{[1
]}

Konovalova, Tatiana ^{[1
]}

Black, Anne ^{[1
]}

Orso, Evelyn ^{[1
]}

Liebisch, Gerhard ^{[1
]}

Ahrens, Maike ^{[2
]}

Eisenacher, Martin ^{[2
]}

Meyer, Helmut E. ^{[3
]}

Schmitz, Gerd ^{[1
]}

机构：

[1] Univ Clin Regensburg, Inst Clin Chem & Lab Med, D-93053 Regensburg, Germany

[2] Ruhr Univ Bochum, Med Proteome Ctr, Bochum, Germany

[3] Leibniz Inst Analyt Sci ISAS, Dortmund, Germany

来源：

TRANSFUSION | 2015年 / 55卷 / 03期

关键词：

TANDEM MASS-SPECTROMETRY; NANOPARTICLE TRACKING ANALYSIS; CELL-DERIVED MICROPARTICLES; ALZHEIMERS AMYLOID-BETA; ALPHA-SYNUCLEIN; HUMAN PLASMA; AMINOPHOSPHOLIPID TRANSLOCASE; PARKINSONS-DISEASE; VASCULAR PATHOLOGY; BRAIN MICROBLEEDS;

D O I：

10.1111/trf.12874

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

BackgroundPlatelets (PLTs) in stored PLT concentrates (PLCs) release PLT extracellular vesicles (PL-EVs) induced by senescence and activation, resembling the PLT storage lesion. No comprehensive classification or molecular characterization of senescence-induced PL-EVs exists to understand PL-EV heterogeneity. Study Design and MethodsPL-EVs from 5-day-stored PLCs from healthy individuals were isolated and subfractionated by differential centrifugation, filtration, and density gradient ultracentrifugation into five PLT microvesicle (PL-MV) subfractions (Fraction [F]1-F5) and PLT exosomes (PL-EXs). PL-EV size, concentration, and composition were analyzed by nanoparticle tracking analysis, flow cytometry, and lipid and protein mass spectrometry. Protein data were verified by Western blot. ResultsPL-EVs showed overlapping mean particle sizes of 180 to 260nm, but differed significantly in composition. Less dense, intermediate, and dense PL-MVs enriched specific lipidomic and proteomic markers related to the plasma membrane, intracellular membranes, PLT granules, mitochondria, and PLT activation. -Synuclein (81% of total) accumulated in F1 and F2, amyloid- (A) precursor protein in F3 and F4 (84%), and apolipoprotein (Apo)E (88%) and ApoJ (92%) in F3 to F5. PL-EXs enriched lipid species and proteins, with high abundance of lipid raft, PLT adhesion, and immune response-related markers. ConclusionDifferential lipid and protein compositions of PL-EVs suggest their unique cellular origins and functions, partly overlapping with PLT granule secretion. Dense PL-MVs might represent autophagic vesicles released during PLT activation and apoptosis and PL-EXs resemble lipid rafts, with a potential role in PLT aggregation and immunity. Segregation of -synuclein and A precursor protein, ApoE, and ApoJ into less dense and dense PL-MVs, respectively, show their differential carrier role of neurologic disease-related cargo.

引用

页码：507 / 521

页数：15

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