title: The first comprehensive and quantitative analysis of human platelet protein composition allows the comparative analysis of structural and functional pathways.
abstract: Antiplatelet treatment is of fundamental importance in combatting functions/dysfunction of platelets in the pathogenesis of cardiovascular and inflammatory diseases. Dysfunction of anucleate platelets is likely to be completely attributable to alterations in posttranslational modifications and protein expression. We therefore examined the proteome of platelets highly purified from fresh blood donations, using elaborate protocols to ensure negligible contamination by leukocytes, erythrocytes, and plasma. Using quantitative mass spectrometry, we created the first comprehensive and quantitative human platelet proteome, comprising almost 4000 unique proteins, estimated copy numbers for ∼ 3700 of those, and assessed intersubject (4 donors) as well as intrasubject (3 different blood samples from 1 donor) variations of the proteome. For the first time, our data allow for a systematic and weighted appraisal of protein networks and pathways in human platelets, and indicate the feasibility of differential and comprehensive proteome analyses from small blood donations. Because 85% of the platelet proteome shows no variation between healthy donors, this study represents the starting point for disease-oriented platelet proteomics. In the near future, comprehensive and quantitative comparisons between normal and well-defined dysfunctional platelets, or between platelets obtained from donors at various stages of chronic cardiovascular and inflammatory diseases will be feasible.
authors.affiliation: Leibniz-Institut für Analytische Wissenschaften-ISAS-e.V., Dortmund, Germany.
authors.forename: Julia M
authors.initials: JM
authors.lastname: Burkhart
authors.forename: Marc
authors.initials: M
authors.lastname: Vaudel
authors.forename: Stepan
authors.initials: S
authors.lastname: Gambaryan
authors.forename: Sonja
authors.initials: S
authors.lastname: Radau
authors.forename: Ulrich
authors.initials: U
authors.lastname: Walter
authors.forename: Lennart
authors.initials: L
authors.lastname: Martens
authors.forename: Jörg
authors.initials: J
authors.lastname: Geiger
authors.forename: Albert
authors.initials: A
authors.lastname: Sickmann
authors.forename: René P
authors.initials: RP
authors.lastname: Zahedi
mesh_terms: D001792:Blood Platelets / Q000737:chemistry* / Q000378:metabolism*; D001798:Blood Proteins / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism*; D002853:Chromatography, Liquid; D015180:Electrophoresis, Gel, Two-Dimensional; D006801:Humans; D011499:Protein Processing, Post-Translational; D020543:Proteome / Q000032:analysis*; D040901:Proteomics; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D001798:Blood Proteins; D020543:Proteome