Atherosclerosis is a chronic, progressive disease affecting the arteries. It involves the buildup of fatty deposits, known as plaques, within the inner lining of arteries. This process leads to hardened and narrowed arteries, which eventually restrict blood flow. The disease often develops silently over many years before causing noticeable symptoms.
The Early Beginnings
Atherosclerosis begins with damage to the endothelium, the inner lining of arteries. This endothelial dysfunction is caused by various factors, including high blood pressure, elevated cholesterol levels, smoking, and high blood sugar. When the endothelium is damaged, it becomes more permeable and no longer effectively prevents the entry of low-density lipoprotein (LDL) particles into the arterial wall.
Once inside the arterial wall, these LDL particles become oxidized, triggering an inflammatory response. This inflammation attracts immune cells, monocytes, from the bloodstream to the site of injury. Monocytes then migrate into the sub-endothelial space and differentiate into macrophages.
Macrophages engulf the oxidized LDL particles, transforming into lipid-laden “foam cells.” These foam cells accumulate within the arterial wall, creating yellowish, flat lesions known as fatty streaks. Fatty streaks are the earliest visible signs of atherosclerosis and often progress to more advanced lesions over time.
Plaque Development and Progression
As atherosclerosis progresses, fatty streaks evolve into more complex, fibrous plaques. This transition involves the accumulation of lipids and a cellular response within the arterial wall. Smooth muscle cells, normally found in the middle layer of the artery, migrate to the inner lining where the fatty streak is located.
These migrating smooth muscle cells proliferate and produce extracellular matrix components, including collagen and elastin. This creates a fibrous cap that covers the lipid-rich core of the plaque. The fibrous cap provides structural stability to the growing lesion.
Within the plaque, calcium also accumulates, leading to calcification. This hardening further contributes to the rigidity of the artery wall. As the plaque grows, it narrows the artery’s lumen, a process known as stenosis, which impedes normal blood flow.
Advanced Disease and Its Consequences
In advanced stages, atherosclerotic plaques become unstable, posing a risk for severe health complications. An unstable plaque is characterized by a thin fibrous cap overlying a large, soft lipid core. Inflammation within the plaque further weakens the fibrous cap, making it more susceptible to rupture.
When an unstable plaque ruptures, the highly thrombogenic material within its core is exposed to the bloodstream. This exposure triggers the formation of a blood clot, or thrombus, on the surface of the ruptured plaque. The thrombus rapidly grows, partially or completely blocking blood flow through the artery.
A complete blockage of blood flow in the coronary arteries, which supply the heart, leads to a heart attack (myocardial infarction). If the blockage occurs in arteries leading to the brain, it results in an ischemic stroke, causing brain cell death. Alternatively, a piece of the thrombus breaks off and travels to other parts of the body, potentially blocking smaller arteries and causing damage, such as in peripheral artery disease, which affects blood flow to the limbs.