The Function and Regulation of Platelet P2Y12 Receptor

Li, Xiaohua; Zhang, Guoxing; Cao, Xia

doi:10.1007/s10557-021-07229-4

Cited by 17 publications

(13 citation statements)

References 180 publications

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“…Unlike the controversial mechanism of aspirin, it is generally believed that P2Y12 receptor antagonists have anti-inflammatory effects [ 37 ]. It has been found in animal models that clopidogrel can also reduce the levels of pro-inflammatory factors such as TNF-α, IL-6, and chemokines in endotoxemia in brain [ 38 , 39 ]. In a study of human systemic inflammation model, it is found that P2Y12 receptor antagonists can reduce platelet aggregation, reduce the peak of pro-inflammatory factors, and inhibit the production of d -dimer [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

High-sensitivity C-reactive protein as a better predictor of post-thrombolytic functional outcome in patients with previous antiplatelet therapy

Wang

et al. 2022

Eur J Med Res

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Background C-reactive protein (CRP) is an important biomarker of inflammation and plays a pivotal role in predicting the clinical prognosis of cardiovascular and cerebrovascular diseases. However, the mechanism of inflammation influencing the outcome of patients with ischemic stroke are unknown. Aims We aim to investigate the association between hsCRP and mRS in 194 eligible patients by therapy-stratified analyses. Methods The modification effects of antiplatelet therapy on the association between mRS and different exposure variables were analyzed. The retained variables were analyzed in the receiver operating characteristic (ROC) curve to discriminate patients with poor outcome. Results hsCRP was positively correlated with mRS in therapy-stratified analyses. There was a statistical modification effect of antiplatelet therapy on the association of hsCRP and mRS (P for interaction = 0.0101). The discriminative effect of poor outcome was further verified by ROC curve analyses (AUCwith from 0.758 to 0.872, AUCwithout from 0.709 to 0.713). Conclusions hsCRP is correlated with the clinical outcome of patients treated with IVrt-PA, and may be a better predictor of post-thrombolytic functional outcome in patients with previous antiplatelet therapy than in non-used patients.

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Section: Discussionmentioning

confidence: 99%

High-sensitivity C-reactive protein as a better predictor of post-thrombolytic functional outcome in patients with previous antiplatelet therapy

Wang

et al. 2022

Eur J Med Res

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“…The cAMP is a negative regulator of platelet adhesion and secretion via activating PKA-induced phosphorylation of vasodilator-stimulated phosphoprotein (VASP). 93 The ADP binding to P2Y 12 not only activates phospholipase C (PLC)-mediated Ca 2+ mobilization but also PI3K-induced integrin αIIbβ3 opening for platelet activation as well as aggregation. This signaling cascade may be interrupted by introducing several P2Y 12 receptor inhibitors.…”

Section: Adp Receptor (P2y 12 ) Inhibitorsmentioning

confidence: 99%

“…P2Y 12 receptor, upon binding with ADP, inhibits the cytoplasmic adenylyl cyclase (AC)‐induced cAMP formation. The cAMP is a negative regulator of platelet adhesion and secretion via activating PKA‐induced phosphorylation of vasodilator‐stimulated phosphoprotein (VASP) 93 . The ADP binding to P2Y 12 not only activates phospholipase C (PLC)‐mediated Ca 2+ mobilization but also PI3K‐induced integrin αIIbβ3 opening for platelet activation as well as aggregation.…”

Section: Synthetic Antiplatelet Molecules For Nddsmentioning

confidence: 99%

Antiplatelet drugs: Potential therapeutic options for the management of neurodegenerative diseases

Beura

Dhapola

Panigrahi

et al. 2023

Medicinal Research Reviews

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The blood platelet plays an important role but often remains under‐recognized in several vascular complications and associated diseases. Surprisingly, platelet hyperactivity and hyperaggregability have often been considered the critical risk factors for developing vascular dysfunctions in several neurodegenerative diseases (NDDs) like Alzheimer's disease, Parkinson's disease, Huntington's disease, and multiple sclerosis. In addition, platelet structural and functional impairments promote prothrombotic and proinflammatory environment that can aggravate the progression of several NDDs. These findings provide the rationale for using antiplatelet agents not only to prevent morbidity but also to reduce mortality caused by NDDs. Therefore, we thoroughly review the evidence supporting the potential pleiotropic effects of several novel classes of synthetic antiplatelet drugs, that is, cyclooxygenase inhibitors, adenosine diphosphate receptor antagonists, protease‐activated receptor blockers, and glycoprotein IIb/IIIa receptor inhibitors in NDDs. Apart from this, the review also emphasizes the recent developments of selected natural antiplatelet phytochemicals belonging to key classes of plant‐based bioactive compounds, including polyphenols, alkaloids, terpenoids, and flavonoids as potential therapeutic candidates in NDDs. We believe that the broad analysis of contemporary strategies and specific approaches for plausible therapeutic treatment for NDDs presented in this review could be helpful for further successful research in this area.

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“…Platelets have a role in regulating inflammation in addition to their role in haemostasis and thrombosis. P2Y12 purine receptor antagonists such as clopidogrel, prasugrel, and ticagrelor are potent antiplatelet and antithrombotic agents that have been widely used for cardiovascular conditions 9 . The importance of the P2Y12 receptor in regulating thrombosis makes it a significant target in research for understanding its regulatory functions.…”

Section: Introductionmentioning

confidence: 99%

P2Y12 receptor residues crucial for thrombosis regulation

Vidhya

2023

J of Molecular Recognition

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Thrombosis, or the formation of blood clots, can lead to serious medical conditions such as stroke, heart attack, and deep vein thrombosis. The purinoreceptor P2Y12 plays a critical role in the thrombotic pathway and is targeted for therapy to prevent clot formation. However, it is essential to balance the regulation of thrombosis to avoid adverse situations. This study focuses on the P2Y12 receptor and aims to discern the protein residue network and differentiate residues based on their intramolecular interactions. The study utilized a statistical analysis to characterize the significant residues involved in ligand interaction, which helps to identify critical residues that are essential for the function of the receptor. A parametric analysis of interactions of residues in the intraprotein interaction was conducted, which revealed significant residue‐based contacts that facilitate protein interactions. By examining the interactions between residues, the mechanisms underlying protein interactions were studied and the importance of specific residues in facilitating these interactions was determined. This research provides important information on P2Y12, and the findings based on the network based significance of interacting residues may contribute to the development of new therapies that target the receptor to prevent clot formation while maintaining a balance in thrombosis regulation to avoid adverse outcomes. Ultimately, this study could lead to improved treatments for thrombotic disorders and better patient outcomes.

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The Function and Regulation of Platelet P2Y12 Receptor

Cited by 17 publications

References 180 publications

High-sensitivity C-reactive protein as a better predictor of post-thrombolytic functional outcome in patients with previous antiplatelet therapy

High-sensitivity C-reactive protein as a better predictor of post-thrombolytic functional outcome in patients with previous antiplatelet therapy

Antiplatelet drugs: Potential therapeutic options for the management of neurodegenerative diseases

P2Y12 receptor residues crucial for thrombosis regulation

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