title: An integrated proteomics and genomics analysis to unravel a heterogeneous platelet secretion defect.
abstract: Eight patients with clinical bleeding problems have evidence for platelet storage pool disease as they present with impaired platelet aggregation and secretion with low concentrations of ADP and collagen and an absence of second phase aggregation with epinephrine. Electron microscopy analysis further showed a reduced but not absent amount of platelet dense granules, and CD63 staining was decreased compared to healthy controls. The presence of alpha granules and CD62P expression after platelet activation was normal. This work aimed at identifying differentially expressed proteins in the platelet releasate and its remaining pellet after activation with A23187 and TRAP in patients and controls using DIGE-based proteomic technology. We identified 44 differentially expressed proteins in patients and the altered expression for some of them was confirmed by immunoblot analysis. Most of these proteins belong to the class of cytoskeleton-related proteins. In addition, 29 cytoskeleton-related genes showed an altered expression in platelet mRNA from patients using a real-time PCR array. In conclusion, our study shows that the dense granule secretion defect in patients with platelet storage pool disease is highly heterogeneous with evidence of an underlying cytoskeleton defect.
authors.affiliation: Center for Molecular and Vascular Biology, University Hospital Leuven, KULeuven, Leuven, Belgium.
authors.forename: Michela
authors.initials: M
authors.lastname: Di Michele
authors.forename: Chantal
authors.initials: C
authors.lastname: Thys
authors.forename: Etienne
authors.initials: E
authors.lastname: Waelkens
authors.forename: Lut
authors.initials: L
authors.lastname: Overbergh
authors.forename: Wannes
authors.initials: W
authors.lastname: D'Hertog
authors.forename: Chantal
authors.initials: C
authors.lastname: Mathieu
authors.forename: Rita
authors.initials: R
authors.lastname: De Vos
authors.forename: Kathelijne
authors.initials: K
authors.lastname: Peerlinck
authors.forename: Chris
authors.initials: C
authors.lastname: Van Geet
authors.forename: Kathleen
authors.initials: K
authors.lastname: Freson
mesh_terms: D000293:Adolescent; D000328:Adult; D001792:Blood Platelets / Q000166:cytology / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D002648:Child; D003594:Cytoplasmic Granules / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics*; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D023281:Genomics; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation; D010981:Platelet Storage Pool Deficiency / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics; D012333:RNA, Messenger / Q000097:blood
chemical_list: D003598:Cytoskeletal Proteins; D012333:RNA, Messenger; D000001:Calcimycin