Atherosclerotic Plaque Formation
Key Components
- LDL particles enter the arterial intima through a process of passive molecular sieving that increases with higher plasma LDL concentrations 1
- Once in the intima, LDL particles become trapped as they are too large to penetrate the elastic laminas of the media 1
- LDL requires modification (e.g., through oxidation) before it can be taken up by macrophages to form foam cells 2
- Oxidized LDL is deposited in macrophages lining the arteries, contributing to foam cell formation 3
- Macrophages are key players in the atherosclerotic process and are recognized as hallmark cells of atherosclerotic plaques 4
- Circulating monocytes transform into macrophages in the arterial wall and take up cholesterol lipoproteins to initiate fatty streaks 5
- Macrophages secrete metalloproteinases and other connective tissue enzymes that can break down collagen, weakening the plaque cap and making it prone to rupture 5
- Activated macrophages accumulate within growing atherosclerotic lesions, contributing to inflammation and plaque progression 5
- Foam cells form when macrophages take up oxidized LDL, becoming filled with indigestible cholesterol droplets 2
Protective Components
- HDL contains apolipoproteins such as apolipoprotein A-I or E, which help remove cholesterol from fatty deposits in the arterial wall 3
- HDL isolated from patients with coronary artery disease lacks endothelial anti-inflammatory properties, suggesting its protective function is impaired in atherosclerosis 3
Pathophysiological Process
- Atherosclerosis begins with injury to the arterial wall caused by factors such as cigarette smoking, hypertension, atherogenic lipoproteins, and hyperglycemia 5
- These injurious factors promote the attachment of monocytes to endothelial cells and their migration into the subintimal space 5
- Monocytes transform into macrophages and take up cholesterol lipoproteins, initiating fatty streak formation 5
- Macrophages and foam cells in atherosclerotic plaques express lipoprotein lipase, which may have a stimulatory role in foam cell formation from triglyceride-rich lipoproteins 2