Abstract
Platelet extracellular vesicles (PEVs) are potential new biomarkers of platelet activation which may allow us to predict and/or diagnose developing coronary thrombosis before myocardial necrosis occurs. The P2Y1 and P2Y12 receptors play a key role in platelet activation and aggregation. Whereas the P2Y1 antagonists are at the preclinical stage, at present, the P2Y12 antagonists are the most effective treatment strategy to prevent stent thrombosis after percutaneous coronary intervention. Despite an increasing number of publications on PEVs, the mechanisms underlying their formation, including the role of purinergic receptors in this process, remain an active research field. Here, we outline the clinical relevance of PEVs in cardiovascular disease, summarize the role and downstream signalling of P2Y receptors in platelet activation, and discuss the available evidence regarding their role in PEV formation.
Highlights
Platelets are anucleated blood cells that play a critical role in haemostasis through their ability to aggregate and form thrombi to stop bleeding [1]
Following binding of adenosine diphosphate (ADP) to the P2Y1 and P2Y12 receptors, ADP triggers an increase in cytoplasmic Ca2+ concentration and a decrease in cytoplasmic cyclic adenosine monophosphate (cAMP) concentration, respectively, promoting platelet activation including the formation of Platelet extracellular vesicles (PEVs)
Based on the insights from signal transduction pathways, it seems that both P2Y1 and P2Y12 receptors may potentially play a role in PEV release because they trigger an increase in cytoplasmic Ca2+ concentration and a decrease in cytoplasmic cAMP concentration, respectively, promoting platelet activation including the formation of PEVs
Summary
Platelets are anucleated blood cells that play a critical role in haemostasis through their ability to aggregate and form thrombi to stop bleeding [1]. In the absence of PGE1, adenosine diphosphate (ADP) released from activated platelets and erythrocytes is one of the most important platelet agonists. There are two main types of receptors that mediate ADP-induced platelet activation: P2Y1 and P2Y12 receptors [5]. Due to the key role of P2Y1 and P2Y12 receptors in platelet activation, specific receptor antagonists have been developed to decrease the risk of arterial thrombosis. Platelet EVs (PEVs) are biomarkers of platelet activation and coronary thrombus formation because PEVs are released from activated platelets and platelet-rich aggregates during early stage thrombosis, which may allow prediction and/or diagnosis of developing coronary thrombosis before the onset of myocardial necrosis or monitoring of the response to treatment with P2Y12 antagonists [16,17]. We outline the clinical relevance of PEVs in cardiovascular disease, summarize the role and downstream signalling of P2Y receptors in platelet activation, and discuss the available evidence regarding their role in PEV formation
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