P2Y 12 Inhibition beyond Thrombosis: Effects on Inflammation

Int J Mol Sci. 2020 Feb 19;21(4):1391. doi: 10.3390/ijms21041391.

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.

Keywords: P2Y12; antiplatelet agents; asthma; atherosclerosis; cancer; hemostasis; inflammation; leukocytes; platelets; sepsis.

Publication types

  • Review

MeSH terms

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

Substances

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