Atherosclerosis
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Direct answer
Atherosclerosis is a chronic, lipid-driven inflammatory disease of the intima of large and medium-sized elastic and muscular arteries, in which fibrofatty plaques narrow the lumen, weaken the media and eventually ulcerate or rupture with superimposed thrombosis. Its pathogenesis follows the response-to-injury sequence: endothelial dysfunction allows LDL entry and oxidation, monocyte-derived macrophages ingest modified lipid through scavenger receptors to become foam cells, and growth-factor signalling drives smooth muscle proliferation and collagen deposition over a lipid core. It is the anatomical basis of ischaemic heart disease, most strokes and peripheral vascular disease.
What you must remember
- Risk factors: non-modifiable are age, male sex and family history; modifiable are smoking, raised LDL cholesterol, hypertension, diabetes and low HDL, with high-sensitivity CRP marking systemic inflammation.
- Core sequence: endothelial injury or dysfunction → LDL insudation and oxidation → monocyte adhesion (VCAM-1) and emigration → macrophage foam cells via unregulated scavenger receptors → fatty streak → smooth muscle migration and proliferation (PDGF) → fibrofatty plaque.
- Fatty streak is the earliest lesion — flat, yellow, intimal aggregates of foam cells seen even in children; most regress, some progress to plaques.
- Mature atheroma: a soft grumous core of necrotic lipid debris, cholesterol clefts and foam cells capped by collagen and smooth muscle, with neovascularisation and frequent calcification.
- Complicated plaque: rupture, ulceration or erosion with overlying thrombosis (the pivot of acute coronary syndromes), intraplaque haemorrhage, calcification and aneurysmal thinning of the wall.
- Vulnerable plaque: thin fibrous cap, large necrotic lipid core, dense macrophage infiltrate and positive (outward) remodelling — often only modestly stenotic yet rupture-prone, unlike the collagen-rich stable plaque with a thick cap and small core.
- Arterial predilection: abdominal aorta worst affected, then coronary arteries (left anterior descending most), popliteal, internal carotid and circle of Willis; internal mammary and radial arteries are spared, hence the mammary artery is the preferred bypass conduit.
Common confusion
Atherosclerosis is often conflated with arteriosclerosis, the umbrella term for arterial hardening. Arteriolosclerosis — hyaline in benign hypertension and diabetes, hyperplastic "onion-skin" in malignant hypertension — is a disease of arterioles, not of the large vessels targeted by atheroma. Monckeberg medial calcific sclerosis is dystrophic calcification of the media of medium muscular arteries in the elderly; it does not narrow the lumen and has no clinical consequence. Atheroma, by contrast, is an intimal, lipid-centred, thrombosis-prone disease of large and medium arteries.
Exam-focused takeaway
NEET-PG tests mechanism and association: identify the foam cell and its scavenger-receptor uptake of oxidised LDL, order the response-to-injury steps, or pick the complication of plaque rupture. One-liners commonly probe the earliest lesion, the composition of plaque core versus cap, the most and least affected arteries, and the strongest modifiable risk factors. This page is the foundation for angina and myocardial infarction, where plaque disruption bridges chronic stenosis and acute events.
Frequently asked questions
What is the earliest lesion of atherosclerosis?
The fatty streak, a flat yellow intimal collection of lipid-laden foam cells, appears even in childhood and is potentially reversible.
How do macrophages turn into foam cells?
They ingest oxidised LDL through scavenger receptors, a pathway not down-regulated by intracellular cholesterol.
Which arteries are characteristically spared?
The internal mammary and radial arteries, which is why the internal mammary artery is the favoured bypass graft.
What makes a plaque vulnerable rather than stable?
A thin cap, bulky lipid core and heavy macrophage content with outward remodelling mark the vulnerable plaque; a thick collagenous cap over a small core defines the stable plaque.
Is atherosclerosis degenerative or inflammatory?
Chronic inflammation: endothelial dysfunction, monocyte recruitment and cytokine-driven injury sustain every stage, from fatty streak to complicated plaque.