Manchester Metropolitan University's Research Repository

    RXR Ligands Negatively Regulate Thrombosis and Hemostasis.

    Unsworth, Amanda J, Flora, Gagan D, Sasikumar, Parvathy, Bye, Alexander P, Sage, Tanya, Kriek, Neline, Crescente, Marilena and Gibbins, Jonathan M (2017) RXR Ligands Negatively Regulate Thrombosis and Hemostasis. Arteriosclerosis, Thrombosis, and Vascular Biology, 37 (5). pp. 812-822. ISSN 1079-5642

    Published Version
    Available under License Creative Commons Attribution.

    Download (1MB) | Preview


    Platelets have been found to express intracellular nuclear receptors including the retinoid X receptors (RXRα and RXRβ). Treatment of platelets with ligands of RXR has been shown to inhibit platelet responses to ADP and thromboxane A2; however, the effects on responses to other platelet agonists and the underlying mechanism have not been fully characterized.The effect of 9-cis-retinoic acid, docosahexaenoic acid and methoprene acid on collagen receptor (glycoprotein VI [GPVI]) agonists and thrombin-stimulated platelet function; including aggregation, granule secretion, integrin activation, calcium mobilization, integrin αIIbβ3 outside-in signaling and thrombus formation in vitro and in vivo were determined. Treatment of platelets with RXR ligands resulted in attenuation of platelet functional responses after stimulation by GPVI agonists or thrombin and inhibition of integrin αIIbβ3 outside-in signaling. Treatment with 9-cis-retinoic acid caused inhibition of thrombus formation in vitro and an impairment of thrombosis and hemostasis in vivo. Both RXR ligands stimulated protein kinase A activation, measured by VASP S157 phosphorylation, that was found to be dependent on both cAMP and nuclear factor κ-light-chain-enhancer of activated B cell activity.This study identifies a widespread, negative regulatory role for RXR in the regulation of platelet functional responses and thrombus formation and describes novel events that lead to the upregulation of protein kinase A, a known negative regulator of many aspects of platelet function. This mechanism may offer a possible explanation for the cardioprotective effects described in vivo after treatment with RXR ligands.

    Impact and Reach


    Activity Overview
    6 month trend
    6 month trend

    Additional statistics for this dataset are available via IRStats2.


    Repository staff only

    Edit record Edit record