Abstract Number: PB1740
Meeting: ISTH 2020 Congress
Background: L-α-lysophosphatidylinositols (LPIs) are bioactive lipid substances involved in the regulation of numerous physiological functions including reproduction, angiogenesis, apoptosis, and inflammation1. LPIs normally persist at nanomolar concentrations in circulating plasma. LPIs have been identified as the first, and currently the only, known endogenous ligands for G protein-coupled receptor 55 (GPR55)2. However, the expression of GPR55 in platelets, and its impact on the modulation of platelet reactivity, thrombosis and haemostasis upon ligation with LPIs under physiological conditions has not yet been investigated.
Aims: This study aims to determine the significance of LPI/GPR55 system in the regulation of platelet function, thrombosis and haemostasis.
Methods: Different species of LPIs (16:0, 17:1, 18:0, 20:4, liver and soy LPIs) and O-1602 (a synthetic ligand for GPR55) were used to investigate their impact on the modulation of platelet reactivity. Diverse concentrations of these molecules were incubated with human and mouse (control and GPR55-/- mice) platelets as either isolated platelets, platelet-rich plasma (PRP) or whole blood, and various platelet functions were analysed.
Results: We have confirmed the presence of GPR55 in human and mouse platelets using immunoblot analysis (Fig 1A). All the LPIs used inhibited platelet activation to various extent (with a minimum concentration < 1 µM) indicating their varying levels of interactions with GPR55 (Fig 1B). Using platelets obtained from GPR55-deficient (Gpr55-/-) mice, we confirmed the absence of this receptor, and the inability of LPIs to inhibit a cross-linked collagen-related peptide (CRP-XL)- induced platelet activation in comparison to controls as measured by the levels of fibrinogen binding (Fig 1C) and p-selectin exposure using flow cytometry. The effects of LPIs were reversed by a GRP55 selective antagonist, CID16020046 (Fig 1D).
Conclusions: LPI/GPR55 system offers novel insights into their potential roles in modulating haemostatic functions of platelets and their significance in the control of platelet reactivity under diverse pathological conditions.
To cite this abstract in AMA style:
Gadd A, Ravishankar D, Vaiyapuri S. Physiological Significance of Lysophosphatidylinositol/G Protein-coupled Receptor 55 System in the Regulation of Platelet Function [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/physiological-significance-of-lysophosphatidylinositol-g-protein-coupled-receptor-55-system-in-the-regulation-of-platelet-function/. Accessed April 18, 2024.« Back to ISTH 2020 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/physiological-significance-of-lysophosphatidylinositol-g-protein-coupled-receptor-55-system-in-the-regulation-of-platelet-function/