title: Apelin: an antithrombotic factor that inhibits platelet function.
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.
authors.affiliation: INSERM, UMR_S 1176, University Paris-Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, France;
authors.forename: Frédéric
authors.initials: F
authors.lastname: Adam
authors.affiliation: University of Bordeaux, INSERM U1029, Pessac, France;
authors.forename: Abdel-Majid
authors.initials: AM
authors.lastname: Khatib
authors.affiliation: INSERM, UMR_S 1176, University Paris-Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, France;
authors.forename: Jose Javier
authors.initials: JJ
authors.lastname: Lopez
authors.affiliation: INSERM U938, Paris, France; University of Pierre et Marie Curie, Unité Mixte de Recherche S938, Paris, France;
authors.forename: Camille
authors.initials: C
authors.lastname: Vatier
authors.affiliation: INSERM, UMR_S 1176, University Paris-Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, France;
authors.forename: Sabrina
authors.initials: S
authors.lastname: Turpin
authors.affiliation: INSERM U938, Paris, France; University of Pierre et Marie Curie, Unité Mixte de Recherche S938, Paris, France;
authors.forename: Adeline
authors.initials: A
authors.lastname: Muscat
authors.affiliation: University of Bordeaux, INSERM U1029, Pessac, France;
authors.forename: Fabienne
authors.initials: F
authors.lastname: Soulet
authors.affiliation: INSERM, UMR_S 1176, University Paris-Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, France;
authors.forename: Anne
authors.initials: A
authors.lastname: Aries
authors.affiliation: Department of Physiology, University of Extremadura, Caceres, Spain;
authors.forename: Isaac
authors.initials: I
authors.lastname: Jardin
authors.affiliation: INSERM, UMR_S 1176, University Paris-Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, France;
authors.forename: Régis
authors.initials: R
authors.lastname: Bobe
authors.affiliation: INSERM, UMR_S 1176, University Paris-Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, France; Assistance Publique-Hôpitaux de Paris, Hospital Lariboisiere, Service d'Hématologie Biologique, Paris, France; University Paris 7 Denis Diderot, Paris, France;
authors.forename: Alain
authors.initials: A
authors.lastname: Stepanian
authors.affiliation: INSERM, UMR_S 1176, University Paris-Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, France; University Paris 7 Denis Diderot, Paris, France; Assistance Publique-Hôpitaux de Paris, Hospital Louis Mourier, Colombes, France;
authors.forename: Dominique
authors.initials: D
authors.lastname: de Prost
authors.affiliation: INSERM U1048, Toulouse, France; University Paul Sabatier, Unité Mixte de Recherche 1048, Toulouse, France; and.
authors.forename: Cédric
authors.initials: C
authors.lastname: Dray
authors.affiliation: Department of Physiology, University of Extremadura, Caceres, Spain;
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Rosado
authors.affiliation: INSERM U1048, Toulouse, France; University Paul Sabatier, Unité Mixte de Recherche 1048, Toulouse, France; and.
authors.forename: Philippe
authors.initials: P
authors.lastname: Valet
authors.affiliation: INSERM U938, Paris, France; University of Pierre et Marie Curie, Unité Mixte de Recherche S938, Paris, France; Hospital Saint-Antoine, Paris, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Feve
authors.affiliation: University of Bordeaux, INSERM U1029, Pessac, France;
authors.forename: Geraldine
authors.initials: G
authors.lastname: Siegfried
mesh_terms: D054392:Adipokines / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D000073861:Apelin; D000075244:Apelin Receptors; D001792:Blood Platelets / Q000378:metabolism*; D006470:Hemorrhage / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D010973:Platelet Adhesiveness; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013917:Thrombin / Q000235:genetics / Q000378:metabolism; D013927:Thrombosis / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control; D013928:Thromboxane A2 / Q000235:genetics / Q000378:metabolism
chemical_list: C115436:APLN protein, human; C104575:APLNR protein, human; D054392:Adipokines; D000073861:Apelin; D000075244:Apelin Receptors; C402826:Apln protein, mouse; C491285:Aplnr protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D043562:Receptors, G-Protein-Coupled; D013928:Thromboxane A2; D013917:Thrombin