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

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.

SUBMITTER: Mendez D

PROVIDER: S-EPMC7503844 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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

Méndez Diego D Arauna Diego D Fuentes Francisco F Araya-Maturana Ramiro R Palomo Iván I Alarcón Marcelo M Sebastián David D Zorzano Antonio A Fuentes Eduardo E

International journal of molecular sciences 20200827 17

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 adhes ...[more]

PMID: 32867213

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Project description:BackgroundContracting skeletal muscle produces reactive oxygen species (ROS) originating from both mitochondrial and cytosolic sources. The use of non-specific antioxidants, such as vitamins C and E, during exercise has produced inconsistent results in terms of exercise performance. Consequently, the effects of the mitochondrial-targeted coenzyme Q10, named Mitoquinone (MitoQ) on exercise responses are currently under investigation.MethodsIn this study, we conducted a meta-analysis to quantitatively synthesize research assessing the impact of MitoQ on aerobic endurance performance and exercise-induced oxidative damage. PubMed, Web of Science, and SCOPUS databases were used to select articles from inception to January 16th of 2024. Inclusion criteria were MitoQ supplementation must be compared with a placebo group, showing acute exercise responses in both; for crossover designs, at least 14 d of washout was needed, and exercise training can be concomitant to MitoQ or placebo supplementation if the study meets the other inclusion criteria points. The risk of bias was evaluated through the Critical Appraisal Checklist (JBI).ResultsWe identified eight studies encompassing a total sample size of 188 subjects. Our findings indicate that MitoQ supplementation effectively reduces exercise-induced oxidative damage (SMD: -1.33; 95% CI: -2.24 to -0.43). Furthermore, our findings indicate that acute and/or chronic MitoQ supplementation does not improve endurance exercise performance (SMD: -0.50; 95% CI: -1.39 to 0.40) despite reducing exercise-induced oxidative stress. Notably, our sensitivity analysis reveals that MitoQ may benefit subjects with peripheral artery disease (PAD) in improving exercise tolerance.ConclusionWhile MitoQ effectively reduces exercise-induced oxidative damage, no evidence suggests that aerobic exercise performance is enhanced by either acute or chronic MitoQ supplementation. However, acute MitoQ supplementation may improve exercise tolerance in subjects with PAD. Future research should investigate whether MitoQ supplementation concurrent with exercise training (e.g., 4-16 weeks) alters adaptations induced by exercise alone and using different doses.

Project description:Introduction: Luteolin inhibits platelet activation and thrombus formation, but the mechanisms are unclear. This study investigated the effects of luteolin on GPVI-mediated platelet activation in vitro and explored the effect of luteolin on thrombosis, coagulation, and platelet production in vivo. Methods: Washed human platelets were used for aggregation, membrane protein expression, ATP, Ca2+, and LDH release, platelet adhesion/spreading, and clot retraction experiments. Washed human platelets were used to detect collagen and convulxin-induced reactive oxygen species production and endogenous antioxidant effects. C57BL/6 male mice were used for ferric chloride-induced mesenteric thrombosis, collagen-epinephrine induced acute pulmonary embolism, tail bleeding, coagulation function, and luteolin toxicity experiments. The interaction between luteolin and GPVI was analyzed using solid phase binding assay and surface plasmon resonance (SPR). Results: Luteolin inhibited collagen- and convulxin-mediated platelet aggregation, adhesion, and release. Luteolin inhibited collagen- and convulxin-induced platelet ROS production and increased platelet endogenous antioxidant capacity. Luteolin reduced convulxin-induced activation of ITAM and MAPK signaling molecules. Molecular docking simulation showed that luteolin forms hydrogen bonds with GPVI. The solid phase binding assay showed that luteolin inhibited the interaction between collagen and GPVI. Surface plasmon resonance showed that luteolin bonded GPVI. Luteolin inhibited integrin αIIbβ3-mediated platelet activation. Luteolin inhibited mesenteric artery thrombosis and collagen- adrenergic-induced pulmonary thrombosis in mice. Luteolin decreased oxidative stress in vivo. Luteolin did not affect coagulation, hemostasis, or platelet production in mice. Discussion: Luteolin may be an effective and safe antiplatelet agent target for GPVI. A new mechanism (decreased oxidative stress) for the anti-platelet activity of luteolin has been identified.

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

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

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