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Apelin: an antithrombotic factor that inhibits platelet function

Frédéric Adam, Abdel-Majid Khatib, Jose Javier Lopez, Camille Vatier, Sabrina Turpin, Adeline Muscat, Fabienne Soulet, Anne Aries, Isaac Jardin, Régis Bobe, Alain Stepanian, Dominique de Prost, Cédric Dray, Juan Antonio Rosado, Philippe Valet, Bruno Feve and Geraldine Siegfried

Key Points

  • Apelin plays a key role in maintaining hemostasis through the regulation of platelet function.

  • Treatment of platelets with apelin inhibits aggregation and thrombus formation.

Abstract

Apelin peptide and its receptor APJ are directly implicated in various physiological processes ranging from cardiovascular homeostasis to immune signaling. Here, we show that apelin is a key player in hemostasis with an ability to inhibit thrombin- and collagen-mediated platelet activation. Mice lacking apelin displayed a shorter bleeding time and a prothrombotic profile. Their platelets exhibited increased adhesion and a reduced occlusion time in venules, and displayed a higher aggregation rate after their activation by thrombin compared with wild-type platelets. Consequently, human and mouse platelets express apelin and its receptor APJ. Apelin directly interferes with thrombin-mediated signaling pathways and platelet activation, secretion, and aggregation, but not with ADP and thromboxane A2-mediated pathways. IV apelin administration induced excessive bleeding and prevented thrombosis in mice. Taken together, these findings suggest that apelin and/or APJ agonists could potentially be useful adducts in antiplatelet therapies and may provide a promising perspective for patients who continue to display adverse thrombotic events with current antiplatelet therapies.

  • Submitted May 28, 2014.
  • Accepted November 19, 2015.
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