Arterial Plaque Formation and Progression

Endothelial Dysfunction

The process initiates with damage to the inner lining of arterial walls, the endothelium. This disruption can result from factors such as elevated levels of low-density lipoprotein (LDL) cholesterol, hypertension, smoking, infections, and inflammatory processes. Compromised endothelial function increases permeability, allowing lipids to enter the arterial wall.

Lipid Accumulation

Following endothelial damage, LDL cholesterol penetrates the intima, the innermost layer of the artery. Once inside, LDL undergoes oxidation. Oxidized LDL triggers an inflammatory response, attracting monocytes from the bloodstream.

Monocyte Recruitment and Macrophage Formation

Monocytes migrate into the intima and differentiate into macrophages. Macrophages ingest oxidized LDL, transforming into foam cells, characterized by their lipid-laden appearance. The accumulation of foam cells represents the early development of a fatty streak.

Fatty Streak Development

Fatty streaks are flat, yellowish lesions on the arterial wall, consisting primarily of foam cells. They represent an early stage and are generally considered reversible at this point. However, persistent risk factors promote the evolution of fatty streaks into more advanced lesions.

Plaque Formation and Growth

Over time, the accumulation of foam cells, cholesterol crystals, and cellular debris forms a plaque. Smooth muscle cells migrate from the media (middle layer of the artery) into the intima and proliferate, contributing to plaque enlargement. These smooth muscle cells also synthesize collagen and other extracellular matrix components, forming a fibrous cap over the lipid-rich core.

Plaque Stability and Vulnerability

Plaques can be classified as either stable or unstable (vulnerable). Stable plaques have a thick fibrous cap and a relatively small lipid core, reducing the risk of rupture. Unstable plaques, conversely, possess a thin fibrous cap and a large lipid core, making them more prone to rupture. The inflammatory activity within the plaque also affects its stability by weakening the fibrous cap.

Plaque Rupture and Thrombosis

Rupture or erosion of an unstable plaque exposes the underlying lipid core and necrotic debris to the bloodstream. This triggers the coagulation cascade, leading to thrombus (blood clot) formation. The thrombus can partially or completely occlude the artery, causing acute ischemic events such as myocardial infarction (heart attack) or stroke.

Arterial Remodeling and Stenosis

Arterial remodeling refers to changes in the artery's size and shape in response to plaque development. Initially, the artery may expand outward (positive remodeling) to accommodate the growing plaque without significantly reducing the vessel lumen. However, as the plaque progresses, the artery eventually undergoes inward remodeling, leading to stenosis (narrowing of the artery). Stenosis restricts blood flow, causing symptoms such as angina (chest pain).