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Review
. 2018 Apr;6(7):e13650.
doi: 10.14814/phy2.13650.

Oxidative Stress and Antioxidant Treatment in Patients With Peripheral Artery Disease

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Free PMC article
Review

Oxidative Stress and Antioxidant Treatment in Patients With Peripheral Artery Disease

Panagiotis Koutakis et al. Physiol Rep. .
Free PMC article

Abstract

Peripheral artery disease is an atherosclerotic disease of arterial vessels that mostly affects arteries of lower extremities. Effort induced cycles of ischemia and reperfusion lead to increased reactive oxygen species production by mitochondria. Therefore, the pathophysiology of peripheral artery disease is a consequence of metabolic myopathy, and oxidative stress is the putative major operating mechanism behind the structural and metabolic changes that occur in muscle. In this review, we discuss the evidence for oxidative damage in peripheral artery disease and discuss management strategies related to antioxidant supplementation. We also highlight the major pathways governing oxidative stress in the disease and discuss their implications in disease progression. Potential therapeutic targets and diagnostic methods related to these mechanisms are explored, with an emphasis on the Nrf2 pathway.

Keywords: Claudication; hydrogen sulfide; nitric oxide; nuclear factor (erythroid-derived 2)-like 2.

Figures

Figure 1
Figure 1
Major pathways governing oxidative stress in PAD. Effort induced cycles of ischemia and reperfusion lead to increased reactive oxygen species production by mitochondria, with the two major sites of ROS production being ETC complexes I and III. The increased ROS production may further cause cumulative mtDNA damage, and progressive ETC dysfunction. Nrf2 may be a key component in attenuating oxidative stress in ischemia‐reperfusion injury. H2S can increase localization of Nrf2, modulating the expression of many antioxidant genes, as well as activation of the HO‐1 signaling pathway.
Figure 2
Figure 2
AGEs formed by oxidative reactions may promote cellular dysfunction and tissue destruction by binding to the RAGE, leading to atherosclerosis and increased arterial stiffness. Pathological effects mediated via RAGE are inhibited by the decoy receptor soluble RAGE (sRAGE).
Figure 3
Figure 3
H2S holds promise as a therapeutic agent in PAD. Via its role in Nrf2 nuclear localization and signaling, H2S may prove to be an important target in combating oxidative stress accompanying the disease. Additionally, H2S regulates eNOS expression and function and increases nitrite reduction to NO, therefore playing a role in atherogenesis.

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