Mitochondrially targeted antioxidants for the treatment of cardiovascular diseases. Recent Pat Cardiovasc Drug Discov 2010 Jan;5(1):54-65
Date
10/08/2009Pubmed ID
19807685DOI
10.2174/157489010790192601Scopus ID
2-s2.0-77951143920 (requires institutional sign-in at Scopus site) 43 CitationsAbstract
Oxidative stress resulting from imbalance between reactive oxygen species (ROS) generation and antioxidant mechanisms is important in the pathogenesis of cardiovascular diseases such as atherosclerosis, ischemic heart disease, heart failure, stroke, hypertension and diabetes. Paradoxically, antioxidant therapy such as vitamin E has not been shown on large randomized clinical trials to favorably affect clinical outcomes. Since mitochondria are involved not only with bioenergetics but also with oxidative damage through ROS generation and cell signaling leading to apoptosis, antioxidants targeted at the mitochondria are appealing novel agents to attenuate oxidative stress. In particular, antioxidants conjugated with triphenylphosphonium cation such as mitoquinone, mitovitamin E and mitophenyltertbutyline achieve concentrations in the mitochondrial matrix several-fold greater than those achieved in the cytosol because of the high negative membrane potential of the inner mitochondrial membrane. We review preliminary experiments and also some patents on cell and animal models of cardiovascular diseases where mitochondrially targeted antioxidants have been used and were shown to reduce ROS production and the effects of oxidative stress due to ROS, apoptosis and improve cardiac function. Although ongoing human clinical studies involve only non-cardiovascular applications at this time, preclinical studies show promise for eventual human trials for cardiovascular diseases.
Author List
Subramanian S, Kalyanaraman B, Migrino RQAuthor
Balaraman Kalyanaraman PhD Professor in the Biophysics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAntioxidants
Apoptosis
Cardiovascular Diseases
Clinical Trials as Topic
Disease Models, Animal
Drug Delivery Systems
Humans
Mitochondria
Oxidative Stress
Patents as Topic
Reactive Oxygen Species