Atherosclerosis

Atherosclerosis is a chronic, progressive disease of large and medium-sized arteries in which lipid, inflammatory cells and fibrous tissue accumulate within the arterial intima to form plaques (atheromas). It is the principal pathological substrate of ischaemic heart disease, most ischaemic strokes and peripheral arterial disease, and is now understood as an inflammatory rather than a purely degenerative process.

Definition

Atherosclerosis is a chronic inflammatory disease of the arterial wall characterised by the intimal accumulation of lipids, macrophage-derived foam cells, smooth-muscle cells and extracellular matrix, forming plaques that narrow the lumen and may rupture or erode to trigger thrombosis.

Scope

The entry covers the formation and evolution of the atherosclerotic plaque - from endothelial injury and lipoprotein retention through fatty streak, fibrous cap and complicated lesion - and the distinction between stable and rupture-prone plaques that links chronic disease to acute events. It is a reference description of pathogenesis and morphology, not clinical management guidance.

Core questions

• How do endothelial dysfunction and lipoprotein retention initiate plaque formation?
• What roles do macrophages, foam cells and smooth-muscle cells play in plaque growth?
• Why do some plaques remain stable while others become rupture-prone?
• How does plaque rupture or erosion convert chronic disease into an acute thrombotic event?

Key concepts

• Endothelial dysfunction
• Low-density lipoprotein retention and oxidation
• Foam cells and the fatty streak
• Fibrous cap and necrotic lipid core
• Vulnerable (rupture-prone) plaque
• Plaque rupture, erosion and thrombosis
• Arterial remodelling

Key theories

Response-to-injury hypothesis

Atherosclerosis is framed as an inflammatory response of the arterial wall to repeated endothelial injury and retained, modified lipoproteins; monocyte recruitment, foam-cell formation and smooth-muscle proliferation build the lesion, replacing the older view of atheroma as passive lipid deposition.

Mechanisms

Disease begins where endothelial dysfunction permits low-density lipoprotein to enter and become retained and modified in the intima. Modified lipoproteins provoke an inflammatory response: monocytes adhere, transmigrate, differentiate into macrophages and ingest lipid to become foam cells, forming the fatty streak. Sustained inflammation recruits smooth-muscle cells that synthesise a fibrous cap over a growing necrotic lipid core. Plaques that combine a large lipid core with a thin, inflamed fibrous cap are mechanically vulnerable; rupture or superficial erosion exposes thrombogenic material to the blood, precipitating luminal thrombosis and acute ischaemic events. The shift from a stenosis-centred to a plaque-biology and inflammation-centred understanding underlies the vulnerable-plaque concept.

Clinical relevance

Atherosclerosis underlies the majority of cardiovascular events, so its biology informs how risk and prevention are understood and how the evidence base is appraised. This entry explains the disease process and the lesion morphology; it is descriptive and not a basis for individual diagnostic or therapeutic decisions.

Epidemiology

As the dominant cause of coronary, cerebrovascular and peripheral arterial disease, atherosclerosis accounts for a large fraction of global cardiovascular morbidity and mortality; its development is shaped by dyslipidaemia, hypertension, smoking, diabetes and other modifiable risk factors.

History

Early twentieth-century work established the lipid content of atheromas, but the modern synthesis came with Ross's response-to-injury hypothesis and its 1999 reframing of atherosclerosis as an inflammatory disease, extended by Libby and colleagues into a detailed inflammatory biology. Pathologists such as Virmani characterised the morphology of the rupture-prone plaque, and the vulnerable-plaque and vulnerable-patient concepts (Naghavi and colleagues, 2003) reoriented thinking from luminal narrowing toward plaque composition and stability.

Debates

Plaque rupture versus plaque erosion

While rupture of a thin-cap fibroatheroma is the classic trigger of coronary thrombosis, a substantial share of events arise from superficial erosion of plaques with intact caps, and the relative contribution and distinct biology of these mechanisms remain under study.

Key figures

• Russell Ross
• Peter Libby
• Renu Virmani
• Goran K. Hansson

Seminal works

• ross-1999
• libby-2002
• virmani-2006

Frequently asked questions

Is atherosclerosis just cholesterol building up in arteries?

No. Lipid accumulation is central, but the modern understanding is that atherosclerosis is a chronic inflammatory disease of the arterial wall in which immune cells, smooth-muscle cells and fibrous tissue all participate in building and complicating the plaque.

What makes a plaque dangerous?

Plaques with a large necrotic lipid core and a thin, inflamed fibrous cap are prone to rupture or erosion; this exposes thrombogenic material and can trigger acute thrombosis, the link between chronic atherosclerosis and acute events like myocardial infarction.