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Current Pharmaceutical Design


ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Targeting Antioxidants to Mitochondria: A Potential New Therapeutic Strategy for Cardiovascular Diseases

Author(s): V. M. Victor and M. Rocha

Volume 13 , Issue 8 , 2007

Page: [845 - 863] Pages: 19

DOI: 10.2174/138161207780363077

Price: $58


Mitochondria produce large amounts of free radicals and play an important role in the life and death of a cell. Thus, mitochondrial oxidative damage and dysfunction contribute to a number of cell pathologies that manifest themselves through a range of conditions including ischemia-reperfusion injury, sepsis, diabetes, atherosclerosis and, consequently, cardiovascular diseases (CVD). In fact, 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 yet clear, oxidative stress seems to play an important role. This review considers the process of CVD from a mitochondrial perspective. Accordingly, strategies for the targeted delivery of antioxidants to mitochondria are being developed. In this review, 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 CVD; currently available antioxidants and possible reasons for their efficacy and inefficacy in ameliorating oxidative stress-mediated diseases; recent developments in mitochondrially-targeted antioxidants that concentrate on the matrix-facing surface of the inner mitochondrial membrane and therefore protect against mitochondrial oxidative damage, and their therapeutic potential for future treatment of CVDs. More pre-clinical and clinical studies, however, are necessary in order to evaluate the effectiveness and toxicity of mitochondrially-targeted antioxidants.

Keywords: Antioxidant, Atherosclerosis, Cardiovascular disease, Endothelium, Mitochondria, Nitric oxide, Oxidative stress, Reactive oxygen species

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