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Mitochondrial Reactive Oxygen Species and Risk of Atherosclerosis

  • Vascular Biology (RS Rosenson, Section Editor)
  • Published:
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Abstract

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.

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Acknowledgments

Funding was provided by the Bijzonder Onderzoeksfonds of the KU Leuven (PF/10/014) and by the Fonds voor Wetenschappelijk Onderzoek-Vlaanderen (G0846.11, and Vascular Biology Network).

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  1. Department of Cardiovascular Sciences, KU Leuven, Atherosclerosis and Metabolism Unit, Herestraat 49, O&N1, PB 705, B-3000, Leuven, Belgium

    Maarten Hulsmans, Els Van Dooren & Paul Holvoet

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  1. Maarten Hulsmans
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  2. Els Van Dooren
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Correspondence to Paul Holvoet.

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Hulsmans, M., Van Dooren, E. & Holvoet, P. Mitochondrial Reactive Oxygen Species and Risk of Atherosclerosis. Curr Atheroscler Rep 14, 264–276 (2012). https://doi.org/10.1007/s11883-012-0237-0

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