Mitoquinone (MitoQ) Inhibits Platelet Activation Steps by Reducing ROS Levels.

Diego Méndez,Ramiro Araya-Maturana,Iván Palomo,Eduardo Fuentes,Marcelo Alarcón,Diego Arauna,David Sebastián,Antonio Zorzano,Francisco Fuentes

doi:10.3390/ijms21176192

Abstract

Platelet activation plays a key role in cardiovascular diseases. The generation of mitochondrial reactive oxygen species (ROS) has been described as a critical step required for platelet activation. For this reason, it is necessary to find new molecules with antiplatelet activity and identify their mechanisms of action. Mitoquinone (MitoQ) is a mitochondria-targeted antioxidant that reduces mitochondrial overproduction of ROS. In this work, the antiplatelet effect of MitoQ through platelet adhesion and spreading, secretion, and aggregation was evaluated. Thus MitoQ, in a non-toxic effect, decreased platelet adhesion and spreading on collagen surface, and expression of P-selectin and CD63, and inhibited platelet aggregation induced by collagen, convulxin, thrombin receptor activator peptide-6 (TRAP-6), and phorbol 12-myristate 13-acetate (PMA). As an antiplatelet mechanism, we showed that MitoQ produced mitochondrial depolarization and decreased ATP secretion. Additionally, in platelets stimulated with antimycin A and collagen MitoQ significantly decreased ROS production. Our findings showed, for the first time, an antiplatelet effect of MitoQ that is probably associated with its mitochondrial antioxidant effect.

Highlights

The association between cardiovascular diseases (CVD) development and mitochondrial damage is well known [1]
Washed platelets incubated with MitoQ 10 μM (4.8% ± 0.8%) significantly increased calcein-negative population compared to a non-treated control group (0.8% ± 0.8%; p < 0.001; Figure 1A)
It was observed that MitoQ 10 μM (12.1% ± 1.9%) induced significant cytotoxicity, referring to the basal control (6.7% ± 0.4%; p < 0.001; Figure 1B)

Summary

Introduction

The association between cardiovascular diseases (CVD) development and mitochondrial damage is well known [1] This mitochondrial dysfunction leads to abnormalities in the respiratory chain, adenosine triphosphate (ATP) synthesis, and increased oxidative stress [2]. Several studies have shown that platelets that develop mitochondrial dysfunction display an enhanced production of reactive oxygen species (ROS) [5,6,7] This mitochondrial ROS generation exerts a central role sensitizing the platelet to increase activation stimulated by a wide variety of agonists (e.g., thrombin, thrombin receptor activator peptide-6 (TRAP-6), U46619 and collagen) [8]. Mitochondrial superoxide production can directly stimulate inflammasome-mediated platelet apoptosis [10]

Methods

Results

Conclusion