The role of platelet P2Y₁₂ receptors in inflammation

Abstract

Inflammation is a complex pathophysiological process underlying many clinical conditions. Platelets contribute to the thrombo‐inflammatory response. Platelet P2Y12 amplifies platelet activation, potentiating platelet aggregation, degranulation and shape change. The contents of platelet alpha granules in particular act directly on leucocytes, including mediating platelet‐leucocyte aggregation and activation via platelet P‐selectin. Much evidence for the role of platelet P2Y12 in inflammation comes from studies of P2Y12 inhibitors such as the thienopyridines clopidogrel and prasugrel, and the cyclopentyltriazolopyrimidine ticagrelor, including in animal and human experimental models. These suggest P2Y12 inhibition reduces markers of inflammation with some evidence this reduces incidence of adverse clinical sequelae during inflammatory conditions. Interpretation is complicated by pleiotropic effects such as of thienopyridines on circulating leucocyte numbers and of ticagrelor on adenosine reuptake. The available evidence suggests P2Y12 as a prominent mediator of inflammation and P2Y12 inhibition as a potentially powerful strategy in a broad range of inflammatory conditions.

Exploring the Landscape of Anti-Inflammatory Trials: A Comprehensive Review of Strategies for Targeting Inflammation in Acute Myocardial Infraction

“…Ticagrelor, an antiplatelet agent, also shows anti-inflammatory effects beyond its primary role, and it is potentially achieved via improvement of vascular function and myocardial perfusion [ 82 ]. Interestingly, the research comparing ticagrelor to clopidogrel has assessed the impact of ticagrelor on CRP levels, which is a marker of inflammation and hints at potential anti-inflammatory actions beyond its antithrombotic effects [ 83 ]. Similarly, angiotensin-converting enzyme (ACE) inhibitors like lisinopril and angiotensin II receptor blockers (ARBs), such as losartan exhibit anti-inflammatory properties, reduce inflammation in the cardiovascular system [ 84 , 85 ].…”

Exploring the Landscape of Anti-Inflammatory Trials: A Comprehensive Review of Strategies for Targeting Inflammation in Acute Myocardial Infraction

“…Ticagrelor, an antiplatelet agent, also shows antiinflammatory effects beyond its primary role, and it is potentially achieved via improvement of vascular function and myocardial perfusion [82]. Interestingly, the research comparing ticagrelor to clopidogrel has assessed the impact of ticagrelor on CRP levels, which is a marker of inflammation and hints at potential anti-inflammatory actions beyond its antithrombotic effects [83]. Similarly, angiotensin-converting enzyme (ACE) inhibitors like lisinopril and angiotensin II receptor blockers (ARBs), such as losartan exhibit antiinflammatory properties, reduce inflammation in the cardiovascular system [84,85].…”

Impact of P2Y12 inhibitors on clinical outcomes in sepsis-3 patients receiving aspirin: a propensity score matched analysis

“…Emerging evidences suggest that P2Y12 inhibitors can improve tissue ischemia uncontrolled immune response in sepsis by inhibiting platelet activation and aggregation, modulating the immune response, and regulating the movement of leukocytes [ 5 , 6 ]. In addition, P2Y12 inhibitors are able to counteract platelet-driven immune responses and inhibit monocyte and macrophage functions directly [ 7 , 8 ]. Ticagrelor also attenuates inflammation by inhibiting adenosine uptake [ 9 ].…”

“…As far as the pharmacodynamic mechanism is concerned, P2Y12 inhibitors fit the pathophysiologic changes of sepsis and have the probability of improving the prognosis. researchers are also optimistic about the application of P2Y12 inhibitors in sepsis [ 7 ]. However, the efficacy of P2Y12 in sepsis remains unclear.…”