title: Platelet proteome and clopidogrel response in patients with stable angina undergoing percutaneous coronary intervention.
abstract: OBJECTIVE
  We analyzed the platelet proteome of circulating platelets during the onset of clopidogrel therapy in patients with stable angina underwent percutaneous coronary intervention in order to investigate the mechanisms that control platelet reactivity and clopidogrel response in this context.
  
  
  METHODS
  Twenty patients were enrolled in this study. Blood samples were collected before coronary angiography (T0), 12 h after 600 mg of clopidogrel (T1) and 24 h after percutaneous coronary intervention (PCI) (T2). Platelet reactivity, Clopidogrel response and proteomic analysis were examined.
  
  
  RESULTS
  Clopidogrel loading dose produced a significant inhibition in all markers of platelet activation in both flow cytometry and aggregation tests. Among the proteins found differentially expressed, eighteen were identified by MS/MS analysis and they resulted involved in the cytoskeleton rearrangement (profilin-1, calpain, α-soluble NSF attachment protein, thrombospondin), in the energetic metabolism (ubiquitin-like modifier-activating enzyme 1, protein-L-isoaspartate-(D-aspartate) O-methyltransferase and nucleoside diphosphate kinase B) and in the oxidative stress (heat shock 70 kDa protein 5 and anti-stress induced phosphoprotein 1.
  
  
  CONCLUSIONS
  The present study provides novel information on platelet proteome changes associated with platelet activation and clopidogrel response. This investigation supports the development of further proteomic studies for the identification of novel platelet biomarkers.
authors.affiliation: Scuola Superiore Sant'Anna, Pisa, Italy. volpi@ifc.cnr.it
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Volpi
authors.forename: Laura
authors.initials: L
authors.lastname: Giusti
authors.forename: Federica
authors.initials: F
authors.lastname: Ciregia
authors.forename: Ylenia
authors.initials: Y
authors.lastname: Da Valle
authors.forename: Gino
authors.initials: G
authors.lastname: Giannaccini
authors.forename: Sergio
authors.initials: S
authors.lastname: Berti
authors.forename: Aldo
authors.initials: A
authors.lastname: Clerico
authors.forename: Antonio
authors.initials: A
authors.lastname: Lucacchini
mesh_terms: D000368:Aged; D060050:Angina, Stable / Q000097:blood / Q000188:drug therapy* / Q000601:surgery*; D015906:Angioplasty, Balloon, Coronary / Q000379:methods*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D015153:Blotting, Western; D000077144:Clopidogrel; D003131:Combined Modality Therapy; D054641:Dual Specificity Phosphatase 2 / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000378:metabolism; D015539:Platelet Activation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D011446:Prospective Studies; D020543:Proteome / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D019007:P-Selectin; D010975:Platelet Aggregation Inhibitors; D020543:Proteome; D000077144:Clopidogrel; D054641:Dual Specificity Phosphatase 2; D013988:Ticlopidine