atherosclerosis is characterised by the accumulation of cholesterol in the walls of the arteries leading to inflammation and localised narrowing of the affected vessels
during the 19th century, virchow proposed that atherosclerois was initated by mechanical injury which caused parts of the blood to be deposited within the arterial wall leading to a local inflammatory response
timeline on discovery of lipid involvement
- 1910 - Windaus discovered large quantities of cholesterol in atheromatous aortas
- Anitchkov and Chalatov showed that atherosclerosis could be induced experimentally by feeding cholesterol to rabbits
- 1950s - American physicist Folfman demonstrated an association between coronary artery disease and raised levels of cholesterol carred in plasma by low density but not high density lipoproteins
- Oliver and Boyd in Edinurhg utilised paper electrophoresis to separate alpha and beta lipoproteins to show the ratio was decreased in men with coronary artery disease
- 1967 - Fredrickson and colleagues at NIH publisehd 5 part article in NEJM describing a novel classification of dyslipiadaemia which led to a decade of productive research in the 1970s leading to advances in lipoprotein metabolism and pathogenesis of atherosclerosis
The Apoproteins in cholesterol transport city
magine the body is a busy city, and cholesterol is like delivery trucks carrying essential supplies (fats) to different locations. But these trucks need addresses to know where to go. This is where Apolipoprotein E (ApoE) comes in—it’s like an address label that helps cholesterol reach the right places.
Now, ApoE comes in three types:
1. ApoE2 – A bit “lazy”; doesn’t deliver well.
2. ApoE3 – The “normal” one; delivers efficiently.
3. ApoE4 – Overactive; delivers too fast, sometimes to the wrong place.
ApoE is mainly found on chylomicron remnants and VLDL (very low-density lipoprotein) particles. It helps:
1. Clear cholesterol from the blood by binding to the liver’s LDL receptor and LRP1 (like scanning a barcode to return an item).
2. Regulate lipid metabolism, ensuring fats are recycled properly.
Most people have ApoE3, which works just fine.
ApoE2 (Weak Delivery) → Type III Hyperlipoproteinaemia
• ApoE2 doesn’t bind well to LDL receptors.
• This causes a build-up of cholesterol-rich remnants (like undelivered packages piling up).
• Leads to Type III Hyperlipoproteinaemia (Familial Dysbetalipoproteinaemia) → High cholesterol and triglycerides, increased heart disease risk.
ApoE4 (Overactive, but in a bad way) → Alzheimer’s & Heart Disease
• ApoE4 clears cholesterol too quickly and may increase inflammation.
• Linked to higher LDL (“bad cholesterol”), increasing heart disease risk.
• Also associated with Alzheimer’s disease → May affect how the brain clears amyloid plaques.