Coenzyme Q10 Upregulates Platelet cAMP/PKA Pathway and Attenuates Integrin αIIbβ3 Signaling and Thrombus Growth.

Abstract

SCOPE:

Platelet 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.

METHODS AND RESULTS:

Using a series of platelet functional assays in vitro, it is demonstrated that CoQ10 reduces human platelet aggregation, granule secretion, platelet spreading, and clot retraction. It is further demonstrated that CoQ10 inhibits platelet integrin αIIbβ3 outside-in signaling. These inhibitory effects are mainly mediated by upregulating cAMP/PKA pathway, where CoQ10 stimulates the A2A adenosine receptor and decreases phosphodiesterase 3A phosphorylation. Moreover, CoQ10 attenuates murine thrombus growth and vessel occlusion in a ferric chloride (FeCl3 )-induced thrombosis model in vivo. Importantly, the randomized, double-blind, placebo-controlled clinical trial in dyslipidemic patients demonstrates that 24 weeks of CoQ10 supplementation increases platelet CoQ10 concentrations, enhances the cAMP/PKA pathway, and attenuates αIIbβ3 outside-in signaling, leading to decreased platelet aggregation and granule release.

CONCLUSION:

Through upregulating 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.

• Authors: Fuli Ya, Xiaohong Ruby Xu, Yilin Shi, Reid C Gallant, Fenglin Song, Xiao Zuo, Yimin Zhao, Zezhong Tian, Cheng Zhang, Xiping Xu, Wenhua Ling, Heyu Ni, Yan Yang
• Journal: Molecular nutrition & food research (Mol Nutr Food Res) Vol. 63 Issue 23 Pg. e1900662 (12 2019) ISSN: 1613-4133 [Electronic] Germany
• PMID: 31512815 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Platelet Glycoprotein GPIIb-IIIa Complex
• Receptor, Adenosine A2A
• Ubiquinone
• Cyclic AMP
• Cyclic AMP-Dependent Protein Kinases
• Cyclic Nucleotide Phosphodiesterases, Type 3
• PDE3A protein, human
• coenzyme Q10

Topics

• Adult
• Animals
• Cyclic AMP (physiology)
• Cyclic AMP-Dependent Protein Kinases (physiology)
• Cyclic Nucleotide Phosphodiesterases, Type 3 (metabolism)
• Double-Blind Method
• Humans
• Male
• Mice
• Mice, Inbred C57BL
• Platelet Aggregation (drug effects)
• Platelet Glycoprotein GPIIb-IIIa Complex (antagonists & inhibitors, physiology)
• Receptor, Adenosine A2A (physiology)
• Signal Transduction (physiology)
• Thrombosis (prevention & control)
• Ubiquinone (analogs & derivatives, pharmacology)
• Up-Regulation