CoenzymeQ10-Induced Activation of AMPK-YAP-OPA1 Pathway Alleviates Atherosclerosis by Improving Mitochondrial Function, Inhibiting Oxidative Stress and Promoting Energy Metabolism

Xie, Tianqi; Wang, Changyuan; Jin, Yue; Meng, Qiang; Liu, Qi; Wu, Jingjing; Sun, Huijun

doi:10.3389/fphar.2020.01034

Cited by 40 publications

(26 citation statements)

References 63 publications

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“…Endothelial mitochondrial dysfunction has been linked to several diseases such as diabetes-induced microvascular injury, cerebral ischemia-reperfusion injury ( Zhang et al, 2020 ), nephropathy ( Zhai et al, 2020 ), peripheral artery disease ( Park et al, 2020 ), and pulmonary artery hypertension ( Wang et al, 2020 ). Many researches have observed the role of mitochondrial damage in triggering endothelial dysfunction upon ox-LDL treatment ( Li et al, 2018 , Li et al, 2020 ; Yuan et al, 2019 ; Xie et al, 2020 ), suggesting an urgent need for therapies that protect endothelial mitochondria in order to reduce atherosclerosis development.…”

Section: Introductionmentioning

confidence: 99%

RETRACTED: Oxidized LDL Causes Endothelial Apoptosis by Inhibiting Mitochondrial Fusion and Mitochondria Autophagy

Zheng¹,

Lu²

2020

Front. Cell Dev. Biol.

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Oxidized low-density lipoprotein (ox-LDL)-induced endothelial dysfunction is an initial step toward atherosclerosis development. Mitochondria damage correlates with ox-LDL-induced endothelial injury through an undefined mechanism. We explored the role of optic atrophy 1 (Opa1)-related mitochondrial fusion and mitophagy in ox-LDL-treated endothelial cells, focusing on mitochondrial damage and cell apoptosis. Oxidized low-density lipoprotein treatment reduced endothelial cell viability by increasing apoptosis. Endothelial cell proliferation and migration were also impaired by ox-LDL. At the molecular level, mitochondrial dysfunction was induced by ox-LDL, as demonstrated by decreased mitochondrial membrane potential, increased mitochondrial reactive oxygen species production, augmented mitochondrial permeability transition pore openings, and elevated caspase-3/9 activity. Mitophagy and mitochondrial fusion were also impaired by ox-LDL. Opa1 overexpression reversed this effect by increasing endothelial cell viability and decreasing apoptosis. Interestingly, inhibition of mitophagy or mitochondrial fusion through transfection of siRNAs against Atg5 or Mfn2, respectively, abolished the protective effects of Opa1. Our results illustrate the role of Opa1-related mitochondrial fusion and mitophagy in sustaining endothelial cell viability and mitochondrial homeostasis under ox-LDL stress.

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Section: Introductionmentioning

confidence: 99%

RETRACTED: Oxidized LDL Causes Endothelial Apoptosis by Inhibiting Mitochondrial Fusion and Mitochondria Autophagy

Zheng¹,

Lu²

2020

Front. Cell Dev. Biol.

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“…It is important, instead, to highlight that the high significant OPA-1 expression level after 12 h of lovastatin treatment is strictly associated with its biological role in the regulation of mitochondrial stability and cellular energy output, as demonstrated in previous studies [ 34 , 35 ]. Indeed, OPA-1 is a mitochondrial fusion protein which is characterized by rigorous cellular regulation, including apoptosis and respiratory capacity, necessary for oxidative phosphorylation (OXPHOS) and ATP production [ 36 , 37 , 38 ].…”

Section: Discussionmentioning

confidence: 99%

MitoQ Is Able to Modulate Apoptosis and Inflammation

Piscianz

Tesser

Rimondi

et al. 2021

IJMS

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Mitoquinone (MitoQ) is a mitochondrial reactive oxygen species scavenger that is characterized by high bioavailability. Prior studies have demonstrated its neuroprotective potential. Indeed, the release of reactive oxygen species due to damage to mitochondrial components plays a pivotal role in the pathogenesis of several neurodegenerative diseases. The present study aimed to examine the impact of the inflammation platform activation on the neuronal cell line (DAOY) treated with specific inflammatory stimuli and whether MitoQ addition can modulate these deregulations. DAOY cells were pre-treated with MitoQ and then stimulated by a blockade of the cholesterol pathway, also called mevalonate pathway, using a statin, mimicking cholesterol deregulation, a common parameter present in some neurodegenerative and autoinflammatory diseases. To verify the role played by MitoQ, we examined the expression of genes involved in the inflammation mechanism and the mitochondrial activity at different time points. In this experimental design, MitoQ showed a protective effect against the blockade of the mevalonate pathway in a short period (12 h) but did not persist for a long time (24 and 48 h). The results obtained highlight the anti-inflammatory properties of MitoQ and open the question about its application as an effective adjuvant for the treatment of the autoinflammatory disease characterized by a cholesterol deregulation pathway that involves mitochondrial homeostasis.

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“…Furthermore, CoQ10 also attenuated the oxLDL-mediated down-regulation of eNOS and the secretion of endothelin 1 (ET-1). It suppressed oxLDL-activated NF-κB and downstream inflammatory mediators, including expression of adhesion molecules, the release of proinflammatory cytokines (ICAM-1, VCAM-1, IL-6, TNF-α and NLRP3) and the adherence of monocytic THP-1 cells [ 107 , 108 , 109 ]. The preventive effects of CoQ10 against atherosclerosis might be achieved by improving mitochondrial function and promoting energy metabolism through the AMPK-YAP-OPA1 pathway [ 109 ].…”

Section: Coq10 Endothelial Dysfunction and Hypertensionmentioning

confidence: 99%

The Use of Coenzyme Q10 in Cardiovascular Diseases

Llanos-González

Alcaı́n

2021

Antioxidants

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CoQ10 is an endogenous antioxidant produced in all cells that plays an essential role in energy metabolism and antioxidant protection. CoQ10 distribution is not uniform among different organs, and the highest concentration is observed in the heart, though its levels decrease with age. Advanced age is the major risk factor for cardiovascular disease and endothelial dysfunction triggered by oxidative stress that impairs mitochondrial bioenergetic and reduces NO bioavailability, thus affecting vasodilatation. The rationale of the use of CoQ10 in cardiovascular diseases is that the loss of contractile function due to an energy depletion status in the mitochondria and reduced levels of NO for vasodilatation has been associated with low endogenous CoQ10 levels. Clinical evidence shows that CoQ10 supplementation for prolonged periods is safe, well-tolerated and significantly increases the concentration of CoQ10 in plasma up to 3–5 µg/mL. CoQ10 supplementation reduces oxidative stress and mortality from cardiovascular causes and improves clinical outcome in patients undergoing coronary artery bypass graft surgery, prevents the accumulation of oxLDL in arteries, decreases vascular stiffness and hypertension, improves endothelial dysfunction by reducing the source of ROS in the vascular system and increases the NO levels for vasodilation.

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CoenzymeQ10-Induced Activation of AMPK-YAP-OPA1 Pathway Alleviates Atherosclerosis by Improving Mitochondrial Function, Inhibiting Oxidative Stress and Promoting Energy Metabolism

Abstract: This study provides a possible new mechanism for CoQ10 in the treatment of AS and may bring a new hope for the prevention and treatment of AS in the future.

Cited by 40 publications

References 63 publications

RETRACTED: Oxidized LDL Causes Endothelial Apoptosis by Inhibiting Mitochondrial Fusion and Mitochondria Autophagy

RETRACTED: Oxidized LDL Causes Endothelial Apoptosis by Inhibiting Mitochondrial Fusion and Mitochondria Autophagy

MitoQ Is Able to Modulate Apoptosis and Inflammation

The Use of Coenzyme Q10 in Cardiovascular Diseases

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