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Glucagon-Like Peptide 1 Receptor Activation Attenuates Platelet Aggregation and Thrombosis

Alison Cameron-Vendrig1, Adili Reheman2, M Ahsan Siraj3

  • 1Department of Physiology, University of Toronto, Toronto, Ontario, Canada Heart and Stroke Richard Lewar Centre of Excellence, University of Toronto, Toronto, Ontario, Canada Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada.

Diabetes
|March 4, 2016
PubMed

Insights

Glucagon-like peptide 1 receptor (GLP-1R) agonists reduce cardiovascular events by inhibiting platelet aggregation and thrombus formation. This study reveals GLP-1R

Area of Science:

  • Cardiovascular Research
  • Endocrinology
  • Pharmacology

Background:

  • Short-term studies suggest GLP-1 targeted therapies reduce cardiovascular events in diabetes patients.
  • The rapid onset of these cardiovascular benefits remains mechanistically unexplained.

Purpose of the Study:

  • To investigate the role of the glucagon-like peptide 1 receptor (GLP-1R) in platelet function and thrombosis.
  • To explore potential mechanisms for the rapid cardioprotective effects of GLP-1R agonists.

Main Methods:

  • Cloned and characterized GLP-1R mRNA expression in human megakaryocyte cell line (MEG-01).
  • Assessed cAMP response and platelet aggregation inhibition by GLP-1 and exenatide in vitro.
  • Evaluated exenatide's effect on thrombus formation in ex vivo and in vivo mouse models, including GLP-1R deficient mice.

Main Results:

  • GLP-1R is expressed in MEG-01 cells, responding to GLP-1 and exenatide with cAMP production.
  • Exenatide significantly inhibited platelet aggregation and thrombus formation in human and mouse blood ex vivo and in vivo.
  • GLP-1R deficiency in bone marrow partially abrogated exenatide's antithrombotic effects, while endothelial nitric oxide synthase deficiency abolished them.

Conclusions:

  • GLP-1R agonists inhibit platelet function and prevent thrombus formation, suggesting a novel mechanism for reducing atherothrombotic events.
  • These findings highlight the direct antithrombotic potential of GLP-1R agonists, contributing to their rapid cardiovascular benefits.

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