OBJECTIVES: 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. DESIGN & METHODS: Twenty patients were enrolled in this study. Blood samples were collected before coronary angiography (T0), 12h after 600mg of clopidogrel (T1) and 24h 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, alpha-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 70kDa 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.
Platelet proteome and clopidogrel response in patients with stable angina undergoing percutaneous coronary intervention.
GIUSTI, LAURA;CIREGIA, FEDERICA;DA VALLE, YLENIA;GIANNACCINI, GINO;LUCACCHINI, ANTONIO
2012-01-01
Abstract
OBJECTIVES: 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. DESIGN & METHODS: Twenty patients were enrolled in this study. Blood samples were collected before coronary angiography (T0), 12h after 600mg of clopidogrel (T1) and 24h 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, alpha-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 70kDa 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
