Atherosclerosis, Mitochondrial Dysfunction and Oxidative Stress: Mitochondria-Targeted Antioxidants as Potential Therapy
Pp. 96-135 (40)
Irene Escribano-Lopez, Noelia Diaz-Morales, Susana Rovira-Llopis, Celia Bañuls, Sandra Lopez-Domenech, Raquel Castelló, Rosa Falcón, Eva Sola, Milagros Rocha, Antonio Hernández-Mijares and Victor M. Víctor
Chronic and acute overproduction of reactive oxygen species (ROS) under
pathophysiologic conditions forms an integral part of the development of cardiovascular
diseases (CVD), and in particular atherosclerosis. These ROS are released from different
sources, such as xanthine oxidase, lipoxygenase, nicotinamide adenine dinucleotide
phosphate oxidase, the uncoupling of nitric oxide synthase and, in particular,
mitochondria. Endothelial dysfunction, characterized by a loss of nitric oxide (NO)
bioactivity, occurs early on in the development of atherosclerosis, and determines future
vascular complications. Although the molecular mechanisms responsible for mitochondriamediated
disease processes are not clear, oxidative stress seems to play an important
role. In general, ROS are essential to cell function, but adequate levels of antioxidant
defenses are required in order to avoid the harmful effects of excessive ROS production.
Mitochondrial oxidative stress damage and dysfunction contribute to a number of cell
pathologies that manifest themselves through a range of conditions. This review considers
the process of atherosclerosis from a mitochondrial perspective, and assesses strategies
for the targeted delivery of antioxidants to mitochondria that are currently under
development. We will provide a summary of the following areas: the cellular metabolism
of reactive oxygen species (ROS) and its role in pathophysiological processes such as
atherosclerosis; currently available antioxidants and possible reasons for their efficacy
and inefficacy in ameliorating oxidative stress-mediated diseases; and recent developments
in mitochondrially-targeted antioxidants that concentrate on the matrix-facing surface of
the inner mitochondrial membrane in order to protect against mitochondrial oxidative
damage, and their therapeutic potential as a treatment for atherosclerosis.
Antioxidant, atherosclerosis, autophagy, cardiovascular disease,
cholesterol, clinical study, diabetes, endothelium, human, insulin resistance,
mitochondria, mitochondrial dynamics, mitoQ, nitric oxide, oxidized-LDL,
reactive oxygen species, reticulum stress, superoxide dismutase, targetedantioxidant,
vitamin C, vitamin E.
University Hospital Doctor Peset, Avda Gaspar Aguilar 90, 46017, Valencia, Spain.