How an atheroma forms: the response-to-injury model step by step
- Mechanism
An atheroma is a chronic inflammatory healing response to injured endothelium and trapped cholesterol in the artery wall.
What it is
Atherosclerosis is best understood as a chronic inflammatory response of the arterial wall to endothelial injury. Injured or dysfunctional endothelium lets LDL enter the intima, where it is retained and oxidised. Monocytes follow, become macrophages and swallow the modified lipid to form foam cells. Cytokines and growth factors from macrophages, T cells and platelets recruit smooth-muscle cells, which build a fibrous cap. Over decades the fatty streak becomes a fibrofatty plaque.
Structure
- Early: fatty streak, flat yellow streaks of foam cells without obstruction; seen even in adolescents.
- Later: fibrofatty atheroma (see the plaque page).
Step by step
- Chronic injury (hyperlipidemia, hypertension, smoking, hyperglycemia, disturbed flow) makes the endothelium dysfunctional.
- LDL crosses into the intima, binds proteoglycans and is oxidised.
- Endothelial adhesion molecules capture monocytes, which enter the intima and become macrophages.
- Macrophages engulf oxidised LDL through scavenger receptors and turn into foam cells.
- Cholesterol crystals and modified lipids activate the inflammasome; cytokines recruit T cells and more monocytes.
- Platelet and macrophage growth factors draw smooth-muscle cells into the intima, where they make collagen.
- A fibrous cap covers a lipid core; dying foam cells enlarge the necrotic core and calcium is deposited.
Clinical notes
- Lowering LDL stabilises and can shrink plaques; anti-inflammatory therapy reduces events in some trials, supporting the inflammatory model.
Test yourself
Think of the answer, then tap the question to see it.
Through which receptors do macrophages take up oxidised LDL?
Scavenger receptors (such as CD36 and SR-A), which are not down-regulated by cholesterol, so lipid keeps accumulating.
Which cell builds the fibrous cap?
Smooth-muscle cells that migrated from the media into the intima and synthesise collagen.
Why do plaques favour branch points?
Disturbed, non-laminar flow there causes endothelial dysfunction; laminar shear stress is protective.
Elsewhere in DurgiPedia
- LDL (low-density lipoprotein)
- Lipoprotein metabolism
- Nitric oxide (NO)
- Monocyte and macrophage
- Cytokines: the table to know
Connections
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Atherosclerosis: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2025); Familial hypercholesterolemia: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2025).
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Representative model, for educational purposes only.