Atherosclerosis I: Introduction

Atherosclerosis is a progressive disorder characterized by accumulation of plaques comprising lipids, calcium, and fibrous tissue within large and medium-sized arteries, causing them to harden and narrow. Development involves multiple factors including hypertension, elevated LDL cholesterol, smoking, and inflammatory conditions that damage the endothelium and allow lipid infiltration.

Foam cells form when monocytes migrate into the damaged arterial wall and transform into macrophages that ingest oxidized LDL cholesterol. These foam cells cluster together to create fatty streaks, marking the earliest visible stage of atherosclerosis and initiating plaque development through continued accumulation and inflammatory responses.

Stable plaques have a thick fibrous cap and restrict blood flow gradually, potentially causing angina. Unstable plaques have a thin fibrous cap that may rupture, attracting platelets and triggering thrombus formation, which can cause myocardial infarction or stroke by suddenly blocking blood flow.

Endothelial damage from hypertension, smoking, elevated LDL, and inflammatory conditions increases arterial wall permeability. This allows circulating lipoproteins to infiltrate the intima, where LDL undergoes oxidation and triggers an inflammatory response that attracts macrophages and initiates plaque formation and progression.

As foam cells accumulate and inflammation persists, plaques enlarge and harden through calcification. Advanced lesions may undergo calcification, which hardens the plaque, reduces arterial elasticity, and increases rupture risk. Smooth muscle cells migrate into the intima and produce extracellular matrix components like collagen, contributing to plaque growth.

When LDL infiltrates the damaged endothelium, it undergoes oxidation and triggers an inflammatory response. This attracts macrophages that transform into foam cells, which accumulate and exacerbate inflammation by releasing cytokines that promote smooth muscle cell migration and proliferation within the arterial intima.

Stable plaques that restrict blood flow can cause angina by reducing oxygen delivery. Ruptured plaques trigger thrombus formation, potentially causing myocardial infarction or stroke. Students should explore atherosclerosis clinical manifestations and diagnostic tests to understand how disease severity is assessed and complications are identified.