P2Y12 Inhibition beyond Thrombosis: Effects on Inflammation.

Abstract

The P2Y12 receptor is a key player in platelet activation and a major target for antithrombotic drugs. The beneficial effects of P2Y12 receptor antagonists might, however, not be restricted to the primary and secondary prevention of arterial thrombosis. Indeed, it has been established that platelet activation also has an essential role in inflammation. Additionally, nonplatelet P2Y12 receptors present in immune cells and vascular smooth muscle cells might be effective players in the inflammatory response. This review will investigate the biological and clinical impact of P2Y12 receptor inhibition beyond its platelet-driven antithrombotic effects, focusing on its anti-inflammatory role. We will discuss the potential molecular and cellular mechanisms of P2Y12-mediated inflammation, including cytokine release, platelet-leukocyte interactions and neutrophil extracellular trap formation. Then we will summarize the current evidence on the beneficial effects of P2Y12 antagonists during various clinical inflammatory diseases, especially during sepsis, acute lung injury, asthma, atherosclerosis, and cancer.

• Authors: Alexandre Mansour, Christilla Bachelot-Loza, Nicolas Nesseler, Pascale Gaussem, Isabelle Gouin-Thibault
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 21 Issue 4 (Feb 19 2020) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 32092903 (Publication Type: Journal Article, Review)

Chemical References

• Anti-Inflammatory Agents
• Cytokines
• Purinergic P2Y Receptor Antagonists
• Receptors, Purinergic P2Y12

Topics

• Acute Lung Injury (drug therapy, metabolism)
• Animals
• Anti-Inflammatory Agents (pharmacology)
• Asthma (drug therapy, metabolism)
• Atherosclerosis (diet therapy, genetics, immunology, metabolism)
• Blood Platelets (drug effects, metabolism)
• Cytokines (metabolism)
• Humans
• Inflammation (drug therapy, immunology, metabolism)
• Neoplasms (drug therapy, immunology, metabolism, pathology)
• Purinergic P2Y Receptor Antagonists (pharmacology, therapeutic use)
• Receptors, Purinergic P2Y12 (chemistry, genetics, metabolism)
• Sepsis (drug therapy, immunology, metabolism, physiopathology)
• Signal Transduction (drug effects, genetics)
• Thrombosis (drug therapy, metabolism)