As is well known to all fans of salad dressing, oil and water don’t like to mix. This creates a problem for the body when it needs to transport fats and oils (collectively called lipids) and the many hormones and vitamins that are fat-soluble. They need to be wrapped up with specialised proteins to create droplets, known as lipoproteins, which can be delivered to tissues by the blood circulation. As lipoproteins travel through the blood, bumping along arteries, they collide with the vessel walls and have a tendency to stick there. Just like a kitchen sink that has had too many greasy pans emptied down it, this build up of fat would eventually cause blockages. Macrophages lining blood vessels play an important role in preventing this. They scavenge the stuck lipoproteins, especially ones containing cholesterol, keeping the vessel walls clean and the blood flowing smoothly.
Although they start out with the best of intentions, the macrophages can end up making the situation worse. Quite how this happens is unclear but understanding it is crucial to tackling cardiovascular disease. Normally the macrophages can recycle the lipoproteins they engulf. Sometimes, due to unhealthy diet or genetic factors, there is more lipid than they can handle and cholesterol builds up inside them in lipid droplets, giving them a foamy appearance under the microscope. These ‘foam cells’ accumulate into a plaque in the blood vessel wall restricting its elasticity and obstructing blood flow. The situation then spirals out of control as the foam cells begin to produce chemical signals which trigger inflammation. This further damages the vessel wall, stimulates more plaque formation and recruits more immune cells which make the inflammation even worse.
At the heart of all this is the key feature of macrophages: their ability to change behaviour from healing and repair to attack and damage. Somehow, becoming engorged with lipids flips this switch so that what began as a healing response leads to swollen cells destroying arteries.
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