Coenzyme Q10 up-regulates Platelet cAMP/PKA Pathway and Attenuates Integrin αIIbβ3 Signaling and Thrombus Growth.

Abstract

SCOPE\nPlatelet integrin αIIbβ3 is the key mediator of atherothrombosis. Supplementation of coenzyme Q10 (CoQ10), a fat-soluble molecule that exists in various foods, exerts protective cardiovascular effects. This study aims to investigate whether and how CoQ10 acts on αIIbβ3 signaling and thrombosis, the major cause of cardiovascular diseases.\n\n\nMETHODS AND RESULTS\nUsing a series of platelet functional assays in vitro, we demonstrated that CoQ10 reduced human platelet aggregation, granule secretion, platelet spreading, and clot retraction. We further demonstrated that CoQ10 inhibited platelet integrin αIIbβ3 outside-in signaling. These inhibitory effects were mainly mediated by up-regulating cAMP/PKA pathway, where CoQ10 stimulated the A2A adenosine receptor and decreased phosphodiesterase 3A phosphorylation. Moreover, CoQ10 attenuated murine thrombus growth and vessel occlusion in a ferric chloride (FeCl3 )-induced thrombosis model in vivo. Importantly, our randomized, double-blind, placebo-controlled clinical trial in dyslipidemic patients demonstrated that 24-weeks of CoQ10 supplementation increased platelet CoQ10 concentrations, enhanced the cAMP/PKA pathway, and attenuated αIIbβ3 outside-in signaling, leading to decreased platelet aggregation and granule release.\n\n\nCONCLUSION\nThrough up-regulating the platelet cAMP/PKA pathway, and attenuating αIIbβ3 signaling and thrombus growth, CoQ10 supplementation may play an important protective role in patients with risks of cardiovascular diseases. This article is protected by copyright. All rights reserved.