Coenzyme Q10 attenuates platelet integrin αIIbβ3 signaling and platelet hyper-reactivity in ApoE-deficient mice
| Autor: | Fuli Ya, Jian-Bo Wan, Xiaohong Ruby Xu, Wenhua Ling, Zezhong Tian, Yan Yang, Reheman Adili, Yilin Shi, Heyu Ni, Yimin Zhao, Fenglin Song, Yinfan Wu, Reid C. Gallant |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Apolipoprotein E Male medicine.medical_specialty Myosin light-chain kinase Platelet Aggregation Mice Knockout ApoE Ubiquinone Integrin Clot Retraction Clot retraction Platelet Glycoprotein GPIIb-IIIa Complex 030204 cardiovascular system & hematology 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Internal medicine medicine Animals Platelet Platelet activation Coenzyme Q10 biology Chemistry General Medicine Atherosclerosis 3. Good health 030104 developmental biology Endocrinology biology.protein Phosphorylation Food Science Signal Transduction |
| Zdroj: | Foodfunction. 11(1) |
| ISSN: | 2042-650X |
| Popis: | 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 a 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 that αIIbβ3-mediated inside-out signaling was attenuated. Additionally, CoQ10 down-regulated platelet αIIbβ3 outside-in signaling including decreasing phosphorylation of the 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 was 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. |
| Databáze: | OpenAIRE |
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