Mitochondria-Targeted Antioxidant MitoQ ₁₀ Improves Endothelial Function and Attenuates Cardiac Hypertrophy

Abstract

Abstract-Mitochondria are a major site of reactive oxygen species production, which may contribute to the development of cardiovascular disease. Protecting mitochondria from oxidative damage should be an effective therapeutic strategy; however, conventional antioxidants are ineffective, because they cannot penetrate the mitochondria. This study investigated the role of mitochondrial oxidative stress during development of hypertension in the stroke-prone spontaneously hypertensive rat, using the mitochondria-targeted antioxidant, MitoQ 10 . Eight-week-old male strokeprone spontaneously hypertensive rats were treated with MitoQ 10 (500 mol/L; nϭ16), control compound decyltriphenylphosphonium (decylTPP; 500 mol/L; nϭ8), or vehicle (nϭ9) in drinking water for 8 weeks. Ϫ goes on to produce a range of damaging ROS that lead to nonspecific modification of mitochondrial proteins, lipids, and nucleic acids, thereby altering mitochondrial function. 3-5 Mitochondrial DNA is particularly susceptible to modification by ROS, and this damage can rapidly lead to functional changes in the cell, because it encodes 13 essential polypeptide components of the mitochondrial respiratory chain. 4 Extensive evidence suggests that mitochondrial DNA damage occurs in cardiovascular disease in humans, animal models, and cellular models. 3,[7][8][9] Mitochondria are normally protected from oxidative damage by a multilayer network of mitochondrial antioxidant systems. 10,11 These include the mitochondrial matrix enzyme manganese superoxide dismutase, which converts the O 2 Ϫ anion to hydrogen peroxide, glutathione peroxidase, and peroxiredoxins 3 and 5, which readily convert hydrogen peroxide to water 7,10 and ultimately prevent forms of mitochondrial oxidative damage, eg, lipid peroxidation. Modification of these antioxidant enzymes resulting from the knockout of manganese superoxide dismutase or glutathione peroxidase genes can significantly affect mitochondrial activity and ROS production and has been linked to hypertension and salt sensitivity in mice. [12][13][14][15] The precise contribution of mitochondria to the total ROS production in the vessel wall or other cardiovascular tissues

Role of mitochondrial dysfunction and altered autophagy in cardiovascular aging and disease: from mechanisms to therapeutics

“…Indeed, the development of antioxidant molecules that achieve concentrations in mitochondria 100-to 1,000-fold higher than in the cytosol, such as Szeto-Schiller (SS) synthetic antioxidant peptides (26,178,179,230), MitoQ (176,205), and Euk-8 (a SOD/catalase mimetic and antioxidant) (94,202), have demonstrated some efficacy in models of cardiovascular stress. A recent study in spontaneous hypertensive rats showed that MitoQ treatment for 8 weeks significantly reduced systolic blood pressure, improved endothelial function, and attenuated cardiac hypertrophy (64). SS-31 has been shown to mitigate I/R injury and reperfusion arrhythmia and preserve myocardial function in various infarct models (reviewed in 179).…”

New insights into the chemistry of Coenzyme Q-0: A voltammetric and spectroscopic study

“…Due to the indispensable function in the processes of oxidative phosphorylation, Coenzyme Q-10 (CoQ-10) and its derivatives are the most prominent members in the family of Q/HQ [4][5][6][7]. Although the number of studies related to the chemical and redox features of CoQ family members has increased tremendously in the last three decades [8][9][10][11][12][13][14][15][16][17][18], many key features are still not well understood. In our last two publications we have shown that Coenzyme Q-1 (CoQ-1) and CoQ-10 undergo structural changes in strong alkaline environment or in the presence of Cytochrome P450 enzymes [19,20].…”

Have No Fear, MitoQ 10 Is Here

“…Moreover, mass spectrometry demonstrated significant ubiquinol content in liver, heart, carotid, and kidney tissues. 6 Conversely, the lipophilic cation used to target ubiquinol to the mitochondria had no beneficial actions. 6 Therefore, the significance of this work is 2-fold.…”

“…6 Conversely, the lipophilic cation used to target ubiquinol to the mitochondria had no beneficial actions. 6 Therefore, the significance of this work is 2-fold. First, it demonstrated the benefits of ubiquinol.…”

“…Another important question raised by the study by Graham et al 6 relates to who can benefit from this formulation of CoQ 10 and what other circumstances would warrant its administration. By demonstrating the salutary actions of MitoQ 10 in stroke-prone spontaneously hypertensive rats, Graham et al 6 demonstrated the beneficial role of CoQ 10 supplementation in a model genetically predisposed to cardiovascular disease and, thus, mitigated the cardiovascular sequelae associated with this particular rodent strain.…”