Molecular Drivers of Platelet Activation: Unraveling Novel Targets for Anti-Thrombotic and Anti-Thrombo-Inflammatory Therapy

Int J Mol Sci. 2020 Oct 24;21(21):7906. doi: 10.3390/ijms21217906.

Abstract

Cardiovascular diseases (CVDs) are the leading cause of death globally-partly a consequence of increased population size and ageing-and are major contributors to reduced quality of life. Platelets play a major role in hemostasis and thrombosis. While platelet activation and aggregation are essential for hemostasis at sites of vascular injury, uncontrolled platelet activation leads to pathological thrombus formation and provokes thrombosis leading to myocardial infarction or stroke. Platelet activation and thrombus formation is a multistage process with different signaling pathways involved to trigger platelet shape change, integrin activation, stable platelet adhesion, aggregation, and degranulation. Apart from thrombotic events, thrombo-inflammation contributes to organ damage and dysfunction in CVDs and is mediated by platelets and inflammatory cells. Therefore, in the past, many efforts have been made to investigate specific signaling pathways in platelets to identify innovative and promising approaches for novel antithrombotic and anti-thrombo-inflammatory strategies that do not interfere with hemostasis. In this review, we focus on some of the most recent data reported on different platelet receptors, including GPIb-vWF interactions, GPVI activation, platelet chemokine receptors, regulation of integrin signaling, and channel homeostasis of NMDAR and PANX1.

Keywords: CXCR; NMDAR; glycoprotein Ib; glycoprotein VI; integrins; pannexin 1; phospholipase D; platelets; reelin.

Publication types

  • Review

MeSH terms

  • Anti-Inflammatory Agents / pharmacology
  • Blood Platelets / metabolism*
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / drug therapy
  • Cardiovascular Diseases / metabolism*
  • Fibrinolytic Agents / pharmacology
  • Gene Regulatory Networks* / drug effects
  • Humans
  • Molecular Targeted Therapy
  • Platelet Activation
  • Platelet Glycoprotein GPIb-IX Complex / metabolism
  • Quality of Life
  • Reelin Protein
  • von Willebrand Factor / metabolism

Substances

  • Anti-Inflammatory Agents
  • Fibrinolytic Agents
  • Platelet Glycoprotein GPIb-IX Complex
  • Reelin Protein
  • von Willebrand Factor
  • RELN protein, human