Provider: Ingenta Connect Database: Ingenta Connect Content: application/x-research-info-systems TY - ABST AU - Victor, V. M. AU - Apostolova, N. AU - Herance, R. AU - Hernandez-Mijares, A. AU - Rocha, M. TI - Oxidative Stress and Mitochondrial Dysfunction in Atherosclerosis: Mitochondria-Targeted Antioxidants as Potential Therapy JO - Current Medicinal Chemistry PY - 2009-12-01T00:00:00/// VL - 16 IS - 35 SP - 4654 EP - 4667 KW - reactive oxygen species KW - nitric oxide KW - antioxidant KW - Atherosclerosis KW - mitochondria KW - endothelium N2 - 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 mitochondria-mediated 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. UR - https://www.ingentaconnect.com/content/ben/cmc/2009/00000016/00000035/art00004 M3 - doi:10.2174/092986709789878265 UR - https://doi.org/10.2174/092986709789878265 ER -