mitoquinone and Cardiovascular-Diseases

Mitochondria are critical for sustaining life, not only as the essential powerhouses of cells but as critical mediators of cell survival and death. Mitochondrial dysfunction has been identified as a key perturbation underlying numerous pathologies including myocardial ischemia-reperfusion injury and the subsequent development of impaired left ventricular systolic function and compensatory cardiac hypertrophy. This article outlines the role of mitochondrial dysfunction in these important cardiac pathologies and highlights current cardioprotective strategies and their clinical efficacy in acute myocardial infarction and heart failure patients. Finally, we explore novel mitochondrial targets and evaluate their potential future translation for clinical cardioprotection.

Topics: Cardiopulmonary Bypass; Cardiotonic Agents; Cardiovascular Diseases; Cell Death; Cyclosporine; Free Radical Scavengers; Humans; Immunosuppressive Agents; Ischemic Postconditioning; Ischemic Preconditioning; Mitochondria, Heart; Mitochondrial Membrane Transport Proteins; Mitochondrial Permeability Transition Pore; Mitophagy; Myocytes, Cardiac; Organophosphorus Compounds; Oximes; Percutaneous Coronary Intervention; Reactive Oxygen Species; Secosteroids; Ubiquinone

Mitochondria have long been known to play a critical role in maintaining the bioenergetic status of cells under physiological conditions. Mitochondria produce large amounts of free radicals, and mitochondrial oxidative damage can contribute to a range of degenerative conditions including cardiovascular diseases (CVDs). Although the molecular mechanisms responsible for mitochondrion-mediated disease processes are not correctly understood, oxidative stress seems to play an important role. Consequently, the selective inhibition of mitochondrial oxidative damage is an obvious therapeutic strategy. This review considers the process of CVD from a mitochondrial perspective and provides a summary of the following areas: reactive oxygen species (ROS) production and its role in pathophysiological processes such as CVD, currently available antioxidants and possible reasons for their efficacy and inefficacy in ameliorating oxidative stress-mediated diseases, and recent developments in mitochondria-targeted antioxidants that concentrate on the matrix-facing surface of the inner mitochondrial membrane. These mitochondrion-targeted antioxidants have been developed by conjugating the lipophilic triphenylphosphonium cation to antioxidant moieties such as ubiquinol. These compounds pass easily through biological membranes and, due to their positive charge, they accumulate several-hundred-fold within mitochondria. In this way they protect against mitochondrial oxidative damage and show potential as a future therapy for CVDs.

Topics: Antioxidants; Cardiovascular Diseases; Diabetes Mellitus; Endothelium, Vascular; Humans; Membrane Potentials; Mitochondria; Mitochondrial Diseases; Nitric Oxide; Organophosphorus Compounds; Oxidative Stress; Reactive Oxygen Species; Reperfusion Injury; Risk Factors; Ubiquinone

Intrauterine growth restriction, a common consequence of prenatal hypoxia, is a leading cause of fetal morbidity and mortality with a significant impact on population health. Hypoxia may increase placental oxidative stress and lead to an abnormal release of placental-derived factors, which are emerging as potential contributors to developmental programming. Nanoparticle-linked drugs are emerging as a novel method to deliver therapeutics targeted to the placenta and avoid risking direct exposure to the fetus. We hypothesize that placental treatment with antioxidant MitoQ loaded onto nanoparticles (nMitoQ) will prevent the development of cardiovascular disease in offspring exposed to prenatal hypoxia. Pregnant rats were intravenously injected with saline or nMitoQ (125 μM) on gestational day (GD) 15 and exposed to either normoxia (21% O

Topics: Age Factors; Animals; Antioxidants; Cardiovascular Diseases; Disease Models, Animal; Female; Fetal Hypoxia; Gestational Age; Hemodynamics; Male; Maternal Exposure; Myocardial Contraction; Nanoparticles; Organophosphorus Compounds; Oxidative Stress; Placenta; Pregnancy; Prenatal Exposure Delayed Effects; Rats, Sprague-Dawley; Sex Factors; Ubiquinone; Ventricular Function, Left

Topics: Animals; Antioxidants; Cardiovascular Diseases; Humans; Hypertension; Mitochondria, Muscle; Myocardium; Organophosphorus Compounds; Oxidation-Reduction; Rats; Reactive Oxygen Species; Tandem Mass Spectrometry; Ubiquinone