Biomedicines (Jun 2020)

Mitochondrial Dysfunction and DNA Damage in the Context of Pathogenesis of Atherosclerosis

  • Taisiia Shemiakova,
  • Ekaterina Ivanova,
  • Andrey V. Grechko,
  • Elena V. Gerasimova,
  • Igor A. Sobenin,
  • Alexander N. Orekhov

DOI
https://doi.org/10.3390/biomedicines8060166
Journal volume & issue
Vol. 8, no. 6
p. 166

Abstract

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Atherosclerosis is a multifactorial disease of the cardiovascular system associated with aging, inflammation, and oxidative stress. An important role in the development of atherosclerosis play elevated plasma lipoproteins. A number of external factors (smoking, diabetes, infections) can also contribute to the development of the disease. For a long time, atherosclerosis remains asymptomatic, therefore, the search for early markers of the disease is critical for the timely management and better outcomes for patients. Mitochondrial dysfunction and mitochondrial DNA (mtDNA) damage appear to connect different aspects of atherosclerosis pathogenesis. To date, multiple lines of research have demonstrated the strong association of mitochondrial dysfunction with the development of various human diseases. Therapies aimed at restoring the mitochondrial function are being actively developed, and are expected to broaden the therapeutic possibilities for several chronic human diseases. The development of such therapies depends on our understanding of the functional roles of different mtDNA variants associated with one or another disorder, and the molecular mechanisms linking mitochondrial dysfunction with a given pathological feature. These questions are, however, challenging and require future intensive research. This review summarizes the recent studies and describes the central processes of the development of atherosclerosis, and shows their relationship with mitochondrial dysfunction. One of the promising therapeutic approaches for future atherosclerosis treatments is the use of mitochondria-targeted antioxidants. Future studies should focus on characterizing the mechanisms of mitochondrial involvement in cardiovascular pathologies to better direct the search for novel therapies.

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