What is Peripheral Arterial Disease (PAD)?

Peripheral arterial disease (PAD) is a common circulatory problem in which narrowed arteries reduce blood flow to the limbs, usually the legs. PAD is typically caused by atherosclerosis, a condition where plaque buildup narrows and stiffens the arteries. When plaque buildup occurs in the arteries supplying blood to the legs, it can lead to symptoms such as leg pain, particularly during physical activity or exercise (intermittent claudication).


What is the relationship between PAD and oxidative stress?

Peripheral arterial disease (PAD) and oxidative stress are closely related, as oxidative stress plays a significant role in the pathogenesis and progression of PAD. Here are some ways in which oxidative stress contributes to PAD:


  • Atherosclerosis Formation: Oxidative stress promotes the formation and progression of atherosclerosis, which is the primary underlying cause of PAD. Reactive oxygen species (ROS) generated during oxidative stress can damage the endothelial lining of blood vessels, leading to inflammation and dysfunction. This endothelial dysfunction allows for the infiltration of lipids, immune cells, and other factors into the arterial wall, initiating the formation of atherosclerotic plaques.


  • Plaque Instability: Oxidative stress contributes to the destabilization of atherosclerotic plaques. ROS can promote the breakdown of collagen and elastin fibers in the plaque, weakening its structure and increasing the risk of rupture or erosion. Plaque rupture can lead to the formation of blood clots (thrombosis) within the artery, further narrowing or blocking blood flow.


  • Vascular Smooth Muscle Cell Proliferation: Oxidative stress stimulates the proliferation and migration of vascular smooth muscle cells within the arterial wall. Excessive proliferation of smooth muscle cells contributes to the thickening of the arterial wall (intimal hyperplasia) and narrowing of the vessel lumen, exacerbating the obstruction of blood flow in PAD.


  • Endothelial Dysfunction: Oxidative stress impairs endothelial function, leading to reduced production of nitric oxide (NO), a vasodilator that helps regulate blood vessel tone and maintain vascular health. Decreased NO bioavailability contributes to vasoconstriction and impaired blood flow in PAD.


  • Inflammation: Oxidative stress promotes inflammation within the arterial wall, contributing to the recruitment and activation of immune cells such as macrophages and T cells. Chronic inflammation exacerbates atherosclerosis and contributes to plaque progression and instability in PAD.


  • Antioxidant Defenses: In PAD, there is often an imbalance between oxidants and antioxidants, with increased production of ROS overwhelming endogenous antioxidant defenses. Dysfunction of antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase further exacerbates oxidative stress and contributes to vascular damage.


Overall, oxidative stress plays a critical role in the pathophysiology of PAD, contributing to atherosclerosis, plaque instability, endothelial dysfunction, smooth muscle cell proliferation, inflammation, and impaired antioxidant defenses.