Platelets are important in processes such as angiogenesis, hemostasis and inflammation. Numerous receptors are present on the platelet membrane which intervene in the processes of adhesion, activation, secretion of granules and platelet aggregation. Among the receptors present on the platelet surface there are the "ADP receptor": P2Y1 mediates a transient increase in cytoplasmic calcium2+, the change in platelet shape and an initial reversible wave of platelet aggregation. P2Y12 amplifies ADP-induced platelet aggregation. Therefore, for normal platelet aggregation to occur, simultaneous activation by ADP is necessary. Unlike P2Y1, P2Y12 has a highly selective tissue distribution and therefore represents an ideal molecular target for pharmacological intervention. Antiplatelet therapy represents the cornerstone treatment of patients suffering from acute coronary syndrome and/or undergoing percutaneous coronary revascularization (PCI) with stent implantation. To date, clopidogrel is the drug of choice in antiplatelet therapy and its effectiveness can be assessed via the VASP test: thanks to the correlation between the phosphorylated intraplatelet VASP protein and the inhibition of the P2Y12 receptor by the drug. As happens with other drugs, the response to clopidogrel is not identical in all patients and there is significant inter-patient variability, therefore this test is very important to understand if the patient is covered by the drug and also allows personalized therapy.
Le piastrine sono importanti in processi come angiogenesi, emostasi ed infiammazione. Sulla membrana piastrinica sono presenti numerosi recettori che intervengono nei processi di adesione, attivazione secrezione dei granuli ed aggregazione piastrinica. Tra i recettori presenti sulla superficie piastrinica ci sono gli “ADP receptor”: il P2Y1 media un incremento transitorio del calcio2+ citoplasmatico, il cambiamento di forma piastrinico e un’iniziale onda reversibile di aggregazione piastrinica. Il P2Y12 amplifica l’aggregazione piastrinica indotta da ADP. Pertanto, perché avvenga una normale aggregazione piastrinica è necessaria l’attivazione contemporanea da parte dell’ADP. Al contrario del P2Y1, il P2Y12 ha una distribuzione tissutale altamente selettiva e pertanto rappresenta un ideale bersaglio molecolare per l’intervento farmacologico. La terapia antiaggregante rappresenta il trattamento cardine dei pazienti affetti da sindrome coronarica acuta e/o sottoposti a rivascolarizzazione coronarica percutanea (PCI) con impianto di stent. Ad oggi il clopidogrel è il farmaco d'elezione nella terapia antiaggregante e la sua efficacia può essere valutata tramite il test VASP: grazie alla correlazione che c'è tra la proteina intrapiastrinica VASP fosforilata e l'inibizione del recettore P2Y12 da parte del farmaco. Come accade per altri farmaci, la risposta al clopidogrel non è identica in tutti i pazienti ed esiste un’importante variabilità interpaziente perciò questo test è molto importante per capire se il paziente è coperto dal farmaco e permette inoltre una terapia personalizzata.
Valutazione dello stato di attivazione della proteina VASP in pazienti in terapia anti-piastrinica: metodi di studio e applicazioni in ambito clinico
FIAMINGO, IRIS
2022/2023
Abstract
Platelets are important in processes such as angiogenesis, hemostasis and inflammation. Numerous receptors are present on the platelet membrane which intervene in the processes of adhesion, activation, secretion of granules and platelet aggregation. Among the receptors present on the platelet surface there are the "ADP receptor": P2Y1 mediates a transient increase in cytoplasmic calcium2+, the change in platelet shape and an initial reversible wave of platelet aggregation. P2Y12 amplifies ADP-induced platelet aggregation. Therefore, for normal platelet aggregation to occur, simultaneous activation by ADP is necessary. Unlike P2Y1, P2Y12 has a highly selective tissue distribution and therefore represents an ideal molecular target for pharmacological intervention. Antiplatelet therapy represents the cornerstone treatment of patients suffering from acute coronary syndrome and/or undergoing percutaneous coronary revascularization (PCI) with stent implantation. To date, clopidogrel is the drug of choice in antiplatelet therapy and its effectiveness can be assessed via the VASP test: thanks to the correlation between the phosphorylated intraplatelet VASP protein and the inhibition of the P2Y12 receptor by the drug. As happens with other drugs, the response to clopidogrel is not identical in all patients and there is significant inter-patient variability, therefore this test is very important to understand if the patient is covered by the drug and also allows personalized therapy.È consentito all'utente scaricare e condividere i documenti disponibili a testo pieno in UNITESI UNIPV nel rispetto della licenza Creative Commons del tipo CC BY NC ND.
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https://hdl.handle.net/20.500.14239/16740