Ten years ago when my father was hospitalised after suffering a heart attack, the nurses gave him a video to watch about heart attacks. The video detailed the symptoms and treatment given, and when addressing the cause of heart attacks, the narrator stated that it is not really known, all is known is that a blood clot arises blocking the artery’s blood flow from reaching the heart, thus starving the heart muscle of vital nutrients and oxygen for survival and ultimately damaging the heart. While the latter is true, the events prior to blood clot formation have been well known for years, in fact centuries! A more accurate statement would have been that it is not fully understood how the various symptoms of a heart attack, such as vomiting and excessive sweating, occur. Nonetheless as an A-level student, this deepened my curiosity into the cause of heart attacks ultimately leading me to undertake a PhD on atherosclerosis – which I will define later in this post.
If you watched the second episode of the recent “Watermen: A Dirty Business” series on BBC Two, you will have seen how drains are often blocked because hundreds of litres of cooking fat is poured down household sinks every week. Over time the fat builds up inside the pipework, particularly at joints and bends, eventually blocking the pipes and causing the rather unpleasant consequence of sewage spewing out onto the roads! The process of fat blocking our sewage pipes is reminiscent of what happens in our own arteries.
So what is the disease inside our arteries that can have such deadly consequences? Firstly it is important to clear up a couple of terms which can cause confusion, even to me! Arteriosclerosis refers to the hardening and thickening of the arterial walls. The middle layer of the artery wall (the tunica media) primarily consists of smooth muscle cells, which contract and relax, like our muscles, to create an elastic effect so that each time the heart pumps, the artery wall expands and constricts to allow pulses of blood to flow through. Hardening of the artery wall means this elasticity is lost and blood pressure increases in the artery. The subsequent narrowing of the artery reduces the ability of blood to flow to the intended tissues.
Hardening can occur for several reasons; calcium deposits can build up in the tunica media. Or a process called intimal hyperplasia can occur (please don’t worry too much about the jargon!) where smooth muscle cells multiply excessively and move towards the inner layer of the artery wall. ‘Intimal’ refers to the innermost layer of the artery – the intima, and ‘hyperplasia’ refers to the excess reproduction or multiplication of cells. Additionally the smooth muscle cells produce proteins such as collagen and elastic fibres further hardening and clogging up the artery.
But the main type of arteriosclerosis causing major problems in the human population, and primarily responsible for heart attacks and strokes, is atherosclerosis. It is a disease that takes decades to develop and inflict its potent consequences on us but by the time we know it’s happening, it is often too late. So what exactly is atherosclerosis? As you read the next part, watch this video which may help you visualise the disease (video created by 3FX medical animation inc.):
Just like the fatty sewage pipes, atherosclerosis begins at bends and branches of arteries. Blood pressure can be high in these regions, and the blood tends to slow down or swirl around causing the cells lining the inside of the artery (called endothelial cells) to become ‘activated’ setting off a chain of events. Firstly ‘lipids’ including cholesterol – particularly low density lipoproteins, more commonly known as ‘bad cholesterol’ - deposit in the artery wall in between the endothelial cells; hence why you should stay away from those pesky fast food outlets! But atherosclerosis is not simply a fatty plaque that blocks your artery. As these lipids slowly build up in the artery, our immune system is called to action by the active endothelial cells and sends in cells called macrophages to consume, break down and dispose of these lipids, and initially they are successful. But over time the amount of lipid building up can become excessive and overwhelm the macrophages, so these cells consume surplus lipid and become immobile, just like if you eat too much chocolate cake and feel so sick you can’t move! The macrophages eventually die and add to the material building up in the artery wall. There are many other types of immune cell that become involved and contribute to the problem but macrophages are the main protagonist (and incidentally the main cell of interest in my research!)
The artery tries to tackle this problem by expanding outwards to increase the diameter of the artery, and by moving smooth muscle cells from the wall to the surface of what is now a developing atherosclerotic plaque. The smooth muscle cells create a ‘cap’ at the surface separating blood flow from the plaque as exposure of dead cells to flowing blood can trigger the formation of a blood clot. Eventually the artery cannot expand any further and so the growing plaque begins to constrict blood flow. The growing plaque can be enough to obstruct blood flow. Narrowing of the artery also causes the flowing blood to exert force on the cap and weaken it eventually causing it to burst open or rupture. A blood clot will then form on the surface, which may or may not block blood flow in the artery. If blood flow is blocked in the coronary arteries supplying blood to heart muscle, a heart attack occurs and some of the heart muscle can die. Alternatively blocking blood flow to part of the brain, either by a blood clot or part of a plaque dislodging and blocking the small blood vessels in the brain, leads to a stroke.
So atherosclerosis is an extremely complex process with many different factors involved, hence why it is so difficult to treat. Research is vital to fully understand this disease and improve existing treatments. Much like cancer, which is so difficult to treat because cancer in each patient can be caused by a different mutation in a different gene, thus we cannot use a ‘one size fits all’ drug.
Now that you know what atherosclerosis is, I will explore how you can reduce your risk of suffering from a heart attack or stroke in my next post.
Dr. Anusha Seneviratne
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.