Platelet proteome and clopidogrel response in patients with stable angina undergoing percutaneous coronary intervention

ObjectivesWe 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 & methodsTwenty 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.ResultsClopidogrel 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.ConclusionsThe 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.

► Antiplatelet drugs represents a debated topic in cardiovascular research.
► Patients with stable angina undergoing PCI were enrolled.
► We used a proteomic approach to study platelet proteome and clopidogrel response.
► Among the proteins found differentially expressed, eighteen were identified.
► These proteins belong to cytoskeleton, energetic metabolism and oxidative stress.