LDL oxidation and foam cell formation in atherosclerosis
Long-lived LDL is oxidised (chemically damaged) in the intima (the innermost layer of the artery wall) and taken up by macrophages, which become foam cells (macrophages packed with lipid).
Remember
LDL that lingers in the blood is more likely to be retained and oxidised in the artery wall, and the macrophages that take it up become the foam cells that start an atherosclerotic plaque.
Memory aid
Long-lived LDL gets oxidised, gets eaten, and turns into foam.
It follows the sequence from long-lived LDL to oxidation, uptake by macrophages and foam cell formation, and it is the macrophage that becomes the foam cell.
Low-density lipoprotein (LDL) is the most cholesterol-rich lipoprotein. It has a long half-life, meaning it stays in the blood for a long time, which gives it more opportunity to enter the intima. The intima is the innermost layer of the artery wall, and it lies under the endothelium (the lining cells). LDL can be retained there.
Retained LDL is oxidised, which means it is chemically damaged. Monocytes (circulating white blood cells) enter the wall and become macrophages, immune cells that engulf debris. Macrophages recognise the damaged LDL with scavenger receptors, a separate set of receptors from the normal LDL receptor.
The normal LDL receptor is switched down as a cell fills with cholesterol, but scavenger receptors are not shut down in that way, so uptake is unregulated. The macrophages keep swelling with cholesterol and become foam cells, named for their foamy look under the microscope.
A collection of foam cells forms a fatty streak, which grows into an atherosclerotic plaque. Over time a plaque can narrow the artery, and a thrombus (blood clot) forming on it can lead to a heart attack or stroke.
A low LDL level is therefore good, since fewer foam cells form and the risk of atherosclerosis falls.
Key facts
- Particle
- LDL is the most cholesterol-rich lipoprotein.
- Long half-life
- LDL stays in the blood for days, which gives it time to be oxidised.
- Site
- excess LDL becomes trapped in the intima, just beneath the endothelium.
- Receptor
- macrophages take up oxidised LDL through scavenger receptors, which are not shut down as the cell fills with cholesterol.
- Result
- the macrophages become foam cells, which form fatty streaks and then atherosclerotic plaques.
- Low LDL
- a low LDL level means fewer foam cells, so the risk of atherosclerosis is reduced.
Exam traps
- Native (unmodified) LDL taken up by the macrophage LDL receptor does not overload macrophages with cholesterol, because that receptor is switched down as cholesterol inside the cell rises. Foam cells form when oxidised LDL enters through scavenger receptors.
- Rapid clearance of LDL by the liver does not raise the risk of atherosclerosis, because it reduces the chance of LDL being oxidised. A long half-life is what raises that risk.
- HDL does not directly deposit cholesterol into the arterial wall. It collects excess cholesterol from body cells and carries it to the liver, and it is traditionally seen as protective.
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