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Coenzyme Q10 attenuates platelet integrin αIIbβ3 signaling and platelet hyper-reactivity in ApoE-deficient mice

Abstract

Coenzyme Q10 (CoQ10) exists in a wide variety of foods and has promising cardiovascular benefits. However, its effects on platelets and integrin αIIbβ3 signaling during atherosclerosis have not been previously explored. Here, apolipoprotein E-deficient (ApoE-/-) mice were fed on the standard diet, high-fat diet (HFD) or CoQ10-supplemented HFD for 12 weeks. We found that CoQ10 supplementation in ApoE-/- mice significantly alleviated formation of HFD-induced atherosclerotic lesions, and attenuated platelet hyper-aggregation and granule secretion, including CD62P, CD63 and CD40 ligand (CD40L) expression and platelet factor-4, β-thromboglobulin and activation normal T cell expressed and secreted (CCL5) release. CoQ10 supplementation decreased soluble fibrinogen and JON/A binding to αIIbβ3 on activated platelets, indicating αIIbβ3-mediated inside-out signaling was attenuated. Additionally, CoQ10 down-regulated platelet αIIbβ3 outside-in signaling including decreasing phosphorylation of β3 intracellular tail, cellular and sarcoma tyrosine-protein kinase (c-Src), and myosin light chain (MLC), and consistently attenuating platelet spreading and clot retraction. Importantly, platelet-monocyte aggregation that primarily mediated by αIIbβ3 and can be blocked using an αIIbβ3 specific antagonist Tirofiban was also markedly diminished by CoQ10. Thus, CoQ10 supplementation attenuates platelet hyper-reactivity via down-regulating both αIIbβ3 inside-out and outside-in signaling, which may play important preventive roles in atherothrombosis. Keywords: Coenzyme Q10, Platelet hyper-reactivity, Integrin αIIbβ3, Atherosclerosis, Apolipoprotein E-deficient mice

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Supplementary files

Publication details

The article was received on 27 Jul 2019, accepted on 22 Oct 2019 and first published on 26 Oct 2019


Article type: Paper
DOI: 10.1039/C9FO01686D
Food Funct., 2019, Accepted Manuscript

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    Coenzyme Q10 attenuates platelet integrin αIIbβ3 signaling and platelet hyper-reactivity in ApoE-deficient mice

    F. Ya, X. R. Xu, Z. Tian, R. C. Gallant, F. Song, Y. Shi, Y. Wu, J. Wan, Y. Zhao, R. Adili, W. Ling, H. Ni and Y. Yang, Food Funct., 2019, Accepted Manuscript , DOI: 10.1039/C9FO01686D

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