Skip to 0 minutes and 4 secondsHello. I'm Dr David Leake. I'd like to tell you about atherosclerosis. Atherosclerosis is the underlying cause of coronary heart disease and thrombotic strokes. It's therefore the main cause of death in the world. So what is atherosclerosis? Well, it' s a bit like water pipes becoming furred up by lime scale. You arteries become furred up so the organs they supply become short of blood, which we called ischemia. The organs affected are mainly the heart muscle, supplied by the coronary arteries, the brain, supplied by arteries in the neck and head, and the legs. Some arteries are spared. For instance, those in the arms aren't affected much. You only get atherosclerosis in large and medium-sized arteries.
Skip to 1 minute and 7 secondsYou don't get it in veins, and that's because arteries have a high blood pressure, whereas veins, of course, have a low blood pressure. So what causes atherosclerosis? Well, as everyone knows, these arteries contain a lot of cholesterol when they become diseased. Now this cholesterol comes from blood, from particles in blood called low density lipoprotein, LDL, or bad cholesterol, as it's often known. LDL gets from the blood into the arterial wall, and there it accumulates. But it's not just about cholesterol. Atherosclerotic lesions are inflammatory sites. It's a bit like a bit of inflamed skin when you get eczema, or inflamed joints in rheumatoid arthritis. Now when arteries become inflamed, blood cells called monocytes pass from the blood into the arterial wall.
Skip to 2 minutes and 18 secondsOnce they get into the arterial wall, they become another cell called a macrophage. That we call differentiation. Now a monocyte is a quiescent, peaceful cell in blood. But once it gets into a tissue like the arterial wall, it can become aggressive, and it can cause damage to tissues if it overstays its welcome. So it's not just cholesterol. The inflammation is important as well. So to go back to cholesterol, why does cholesterol from LDL accumulate in the arterial wall? We think that once LDL gets into the arterial wall, it aggregates. It clumps together.
Skip to 3 minutes and 8 secondsIn the arterial wall, you've got lots of enzymes because they're inflammatory sites. And these enzymes can attack LDL so it becomes unstable. One of the main candidates is called sphingomyelinase, quite a long word. Sphingomyelinase attacks LDL and it aggregates. And then macrophages will engulf the aggregated LDL, draw it into the cell, and then it goes to organelles called lysosomes. Now lysosomes are the acidic stomach of the cell, and they contain iron. And what we think may go on, from work done at the University of Reading, is that once the LDL gets into a lysosome, due to the acidity and the iron, it becomes oxidised.
Skip to 4 minutes and 4 secondsAs you know, if you leave your milk in the fridge for too long, it becomes rancid. That's an oxidation process. And we think the same thing occurs in the arterial wall. Your LDL becomes rancid, and that can cause problems for the arterial wall. What type of atherosclerotic lesions do you get? Well, if you've reached the age of puberty, you've got them already. You've got lesions in your arteries called fatty streaks. But don't worry. They don't cause any problems. Over years and decades, however, they develop. They become bigger and more complex. And then they may cause problems. In older people, you get a type of atherosclerotic lesion called an atheroma.
Skip to 4 minutes and 55 secondsNow these are large lesions, and they've got what's called a necrotic core at their centre. So macrophages in the smooth muscle cells in the arterial wall have died, and they have fragmented. And their fragments make up this necrotic core in the central of the lesion. That's surrounded by what's called a fibrous cap. So you've got this fibrous cap between the necrotic core and the blood. Now if this fissures, it can cause problems because blood enters the lesion. It can clot and form a thrombus. And if you're unlucky, that can block the blood vessel and cause a heart attack or a thrombotic stroke.
Dr David Leake introduces atherosclerosis, a condition that can be described as the “furring” up of the arteries like limescale in pipes, which can lead to ischaemia - a shortness of blood supply to the body’s tissues.
Atherosclerotic arteries usually contain a lot of cholesterol, a risk factor we will learn more about in Week 4. We will look at different types of lesions and how they develop, from fatty streaks during puberty, to atheromas and finally how they can rupture to trigger clot formation.
You can download the Week 2 supplement, which contains additional images and descriptions to help you understand the topics covered in this video.