High levels of
reactive oxygen species (ROS) are observed in chronic human diseases such as
obesity,
type 2 diabetes,
atherosclerosis, and
cardiovascular diseases. In addition to the presence of oxidative stress, these diseases are also characterized by deregulated inflammatory responses. Our first aim is to discuss distinct molecular pathways that determine the rate of mitochondrial ROS (mtROS) production and identify agents and
enzymes that disrupt the balance between ROS generation and ROS elimination. Recent studies exploring the mechanisms linking ROS and
inflammation found that ROS derived from mitochondria act as signal-transducing molecules that provoke endothelial dysfunction associated with uncoupling of
nitric oxide synthase, induce the infiltration and activation of inflammatory cells, and increase apoptosis of endothelial and vascular smooth muscle cells. Therefore, our second aim is to give a comprehensive overview of the role of mtROS in all these processes contributing to atherosclerotic lesion progression and causing plaque erosion and
rupture. Our third aim is to emphasize the role of the inflammatory
toll-like receptor 2/NF-κB signaling pathway in the induction of pro-inflammatory
cytokines and mtROS production in relation to
insulin resistance,
type 2 diabetes, and
atherosclerosis. Because mtROS play an active role in several pathogenic mechanisms there is need for mitochondria-targeted
antioxidants. Preliminary experiments in cell and animal models of
cardiovascular diseases showed that some mitochondria-targeted
antioxidants indeed reduce ROS production. However, wide-spread use in humans requires the development of specific and sensitive assays to evaluate mitochondrial oxidative stress and the development of orally active compounds.