Pathophysiology of Peripheral Arterial Disease (PAD): A Review on Oxidative Disorders

Abstract

Peripheral arterial disease (PAD) is an atherosclerotic disease that affects a wide range of the world’s population, reaching up to 200 million individuals worldwide. PAD particularly affects elderly individuals (>65 years old). PAD is often underdiagnosed or underestimated, although specificity in diagnosis is shown by an ankle/brachial approach, and the high cardiovascular event risk that affected the PAD patients. A number of pathophysiologic pathways operate in chronic arterial ischemia of lower limbs, giving the possibility to improve therapeutic strategies and the outcome of patients. This review aims to provide a well detailed description of such fundamental issues as physical exercise, biochemistry of physical exercise, skeletal muscle in PAD, heme oxygenase 1 (HO-1) in PAD, and antioxidants in PAD. These issues are closely related to the oxidative stress in PAD. We want to draw attention to the pathophysiologic pathways that are considered to be beneficial in order to achieve more effective options to treat PAD patients.

Molecular Mechanisms Associated with ROS-Dependent Angiogenesis in Lower Extremity Artery Disease

“…The pathophysiology of atherosclerotic plaque involves complex interactions between cholesterol metabolism and vascular cell activity. It is also known that disturbance of the laminar arterial flow in PAD plays an essential role in the adhesion of inflammatory blood cells to the arterial wall and plays a role in plaque generation [ 14 ]. The hemodynamic consequences of atherosclerotic plaque depend on the degree of stenosis/occlusion.…”

“…A narrowed vessel progresses towards chronic total occlusion. LEAD patients demonstrate high grades of inflammation and active oxidative stress, which are vital mechanisms in PAD pathophysiology [ 14 ]. There is an interest in the vaso-protective effects of heme oxygenase 1 (HO-1) as a potential antioxidant by affecting the proliferation, migration, and adhesion of smooth vascular muscle cells, endothelial cells, and leukocytes [ 15 ].…”

“…There is an interest in the vaso-protective effects of heme oxygenase 1 (HO-1) as a potential antioxidant by affecting the proliferation, migration, and adhesion of smooth vascular muscle cells, endothelial cells, and leukocytes [ 15 ]. It was previously suggested that PE acts on endothelial functions by regulating genes involved in modulating oxidative metabolism, cell apoptosis, cell growth and proliferation, and endothelial vascular nitric oxide synthase (eNOS) [ 14 , 16 ].…”

Importância do destreinamento físico sobre a capacidade funcional em indivíduos com doença arterial obstrutiva crônica periférica: estudo transversal piloto

“…Functional capacity is reduced in chronic peripheral arterial occlusive disease (PAOD) because of the atherosclerotic process involving the peripheral arteries, 1 with consequent obstruction of the blood flow to the lower limbs, provoking the classic symptom known as intermittent claudication. 2 The shorter the distance an individual can walk before claudication sets in, i.e.…”

O Paradoxo da Intensidade do Exercício Físico na Prevenção de Eventos Cardiovasculares na Doença Arterial Obstrutiva Periférica

“…In 30 RCTs, including 1816 patients with IC, pain-free walking distance and MWD increased on average 82 and 109 meters, respectively, in up to two years. [4][5][6][7][8][9] A meta-analysis of 25 randomized studies (1,054 patients) addressing exercise strategies in the rehabilitation of patients with PAD, found that supervised treadmill exercise was better than the control group, with a gain of 128 meters in pain-free walking distance and 180 meters at the maximum walking distance. In contrast, 3 RCTs (n=493) with PAD found that home walking exercises, when combined with behavior change techniques, improved the 6-minute walking test distance more than interventions on a supervised treadmill (45-54 meters vs. 33-35 meters, respectively).…”