3rd June 2026

Aetiology and Pathophysiology

The underlying mechanism of atherosclerosis is one of endothelial dysfunction. Damage is undertaken on the intima, which may be caused by stress at vessel bifurcations. This endothelial damage leads to a decrease in the bioavailability of nitric oxide and an increase in the amount of reactive oxygen species that are produced. This is made worse by factors such as dyslipidaemia and hypertension. 

LDL cholesterol moves into the arterial wall at the site of the damage, leading to formation of a fatty streak as macrophages cross the endothelium to enter the subintimal space. Smooth muscle cells follow and collagen proliferates, leading to a plaque/ fibrous cap developing. A necrotic core develops within the plaque, containing oxidised cholesterol, secondary to the foam cell accumulation. 

The plaque growth not only narrows the arterial lumen, leading to restricted blood flow and ischaemia, but also risks rupture, in turn leading to blood clot formation. These clots can then lead to life-threatening conditions such as MIs, Transient ischemic attacks (TIAs) and ischaemic strokes.

Table 1. The 3 stages of atherosclerosis summarised

Key features of an atherosclerotic plaque are: 

• Proliferation of macrophages, fibroblasts and smooth muscle cells 
• Deposition of lipids 
• High levels of collagen 
• Necrosis 

Once a certain vascular territory is damaged by atherosclerosis, the total risk for any CV event is much higher, as well as in the organ that is damaged by the compromised blood flow.