Oxidative Stress and Arterial Dysfunction in Peripheral Artery Disease.

Ahmed Ismaeel,Robert Brumberg,Jeffrey Kirk,Evlampia Papoutsi,Ian Sawicki,Robert Smith,Patrick Farmer,Jack Eidson,William Bohannon,Panagiotis Koutakis

doi:10.3390/antiox7100145

Abstract

Peripheral artery disease (PAD) is an atherosclerotic disease characterized by a narrowing of the arteries in the lower extremities. Disease manifestations are the result of more than just reduced blood flow, and include endothelial dysfunction, arterial stiffness, and inflammation. Growing evidence suggests that these factors lead to functional impairment and decline in PAD patients. Oxidative stress also plays an important role in the disease, and a growing amount of data suggest a link between arterial dysfunction and oxidative stress. In this review, we present the current evidence for the involvement of endothelial dysfunction, arterial stiffness, and inflammation in the pathophysiology of PAD. We also discuss the links between these factors and oxidative stress, with a focus on nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2)-derived reactive oxygen species (ROS) and decreased nitric oxide (NO) bioavailability. Finally, the potential therapeutic role of NOX2 antioxidants for improving arterial function and functional status in PAD patients is explored.

Highlights

Peripheral artery disease (PAD) is an atherosclerotic disease characterized by a narrowing of the arteries in the lower extremities [1]
The studies included in this review suggest that reduced nitric oxide (NO) synthesis and activity in PAD may be the result of enhanced oxidative stress, and this in turn may lead to endothelial dysfunction, arterial stiffness, and inflammation
Evidence suggests that endothelial dysfunction and arterial stiffness may be implicated in PAD

Summary

Introduction

Peripheral artery disease (PAD) is an atherosclerotic disease characterized by a narrowing of the arteries in the lower extremities [1]. PAD may be asymptomatic or symptomatic, and the spectrum of symptoms is classified according to the Rutherford classification [2]. Stage 0 is considered asymptomatic, and patients presenting with mild or moderate claudication, or walking-induced leg muscle pain relieved by rest, are classified in Stages 1 and 2, respectively. In the later stages of PAD, patients exhibit foot pain at rest (Stage 4), and/or ulcers and gangrene (Stages 5 and 6) [2]. There is a clear myopathy present in skeletal muscle of PAD patients, which is characterized by abnormal skeletal muscle function and morphology, as well as metabolic defects [3]. The walking impairment in PAD is believed to involve these abnormal muscle

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