Abstract 518: Antithrombotic Effects of Apelin: Implication During Metabolic Disorders

Abstract

Thrombotic risk, that is partly related to a disturbed adipokine/cytokine profile, is strongly increased in obese and type 2 diabetic patients and. Apelin is an adipokine with pleiotropic function and cardiovascular fluid, and energetic homeostasis, and acts through the APJ transmembrane receptor. In this project, we show for the first time that apelin displays a potent antithrombotic effect The antithrombotic effect is APJ- mediated and requires the proteolytic maturation of apelin. Apelin strongly inhibits thrombin- or collagen- induced platelet aggregation, independently of ADP secretion. It prevents platelet activation and thrombin-activated intracellular signaling pathways. As a consequence, in mice models, intravenous apelin injection increases tail-bleeding time and delays chemically- induced vessel occlusion and thrombus stabilization. We also determined that functional APJ is strongly over-expressed in platelet from obese subjects or mice (DIO mice, db/db), but apelin preserved its antithrombotic function during these metabolic disorder conditions. In conclusion, in this original study, we enlighten a new biological function of apelin that could be considered as a new strategy to reduce the increased risk of thrombosis in patients with metabolic disorders.