What is atherosclerosis?

Atherosclerosis is a condition characterized by the buildup of plaque (composed of cholesterol, fats, calcium, and other substances) inside the arteries. It is a progressive disease that can develop over many years and can affect arteries throughout the body, including those supplying blood to the heart (coronary arteries), brain, legs, and other organs.


The development of atherosclerosis begins with damage to the inner lining of the artery, known as the endothelium. This damage can be caused by various factors, including high blood pressure, smoking, high cholesterol levels, diabetes, and inflammation. Once the endothelium is damaged, it becomes more permeable to substances such as low-density lipoprotein (LDL) cholesterol, which can penetrate the artery wall and accumulate.


Over time, the accumulated LDL cholesterol and other substances form plaque deposits, which can narrow the artery and restrict blood flow. This narrowing of the arteries can reduce blood flow to vital organs and tissues, leading to various complications, depending on the location of the affected arteries. For example:


  • Coronary artery disease: Atherosclerosis in the coronary arteries can lead to reduced blood flow to the heart muscle, causing chest pain (angina) or, in severe cases, a heart attack (myocardial infarction).


  • Carotid artery disease: Atherosclerosis in the carotid arteries supplying blood to the brain can increase the risk of stroke or transient ischemic attack (TIA), also known as a “”mini-stroke.””


  • Peripheral artery disease: Atherosclerosis in the arteries supplying blood to the legs and feet can cause symptoms such as leg pain, numbness, weakness, or ulcers, especially during physical activity.


What is the relationship between atherosclerosis and oxidative stress?

Oxidative stress plays a crucial role in the development and progression of the disease.


  • Endothelial Dysfunction: Oxidative stress can lead to dysfunction of the endothelial cells lining the arteries, making them more susceptible to damage. When the endothelium is damaged, it becomes more permeable to LDL cholesterol and other substances, which can penetrate the artery wall and initiate the formation of plaque.


  • LDL Oxidation: Oxidative stress promotes the oxidation of LDL cholesterol particles, turning them into oxidized LDL (oxLDL). OxLDL is more potent than native LDL in promoting inflammation and endothelial dysfunction, contributing to the development of atherosclerosis.


  • Inflammation: Oxidative stress can trigger inflammatory responses within the artery wall, leading to the recruitment of immune cells such as macrophages and T cells. These immune cells release pro-inflammatory cytokines and reactive oxygen species, further exacerbating oxidative stress and promoting the formation and progression of plaque.


  • Smooth Muscle Cell Proliferation: Oxidative stress can stimulate the proliferation and migration of smooth muscle cells within the artery wall, contributing to the thickening of the arterial intima and the formation of atherosclerotic lesions.


  • Foam Cell Formation: Oxidized LDL and inflammatory cytokines can promote the transformation of macrophages into foam cells, which are lipid-laden cells that accumulate within the artery wall and contribute to the development of plaque.


  • Endothelial Nitric Oxide (NO) Bioavailability: Oxidative stress can reduce the bioavailability of nitric oxide (NO), a molecule produced by endothelial cells that helps regulate blood vessel tone and prevent platelet aggregation. Reduced NO bioavailability can impair endothelial function and promote vasoconstriction, inflammation, and thrombosis, further contributing to atherosclerosis.


Overall, oxidative stress is a central mechanism underlying the pathogenesis of atherosclerosis. It promotes endothelial dysfunction, inflammation, smooth muscle cell proliferation, foam cell formation, and other processes involved in plaque formation and progression.