Skip to 0 minutes and 10 seconds DANIEL MALONE: In this section, you will learn what hyperlipidemia and atherosclerosis are, observe how lipids are transported around the body, and see why atherosclerosis increases the risk of diseases such as heart disease. Hyperlipidemia is defined as an increase in blood concentrations of lipids, more commonly termed fats. Lipids are molecules that share a common property of not being able to dissolve in water. Cholesterol and triglycerides are two types of lipids found in the blood, and either or both of these lipids are raised in the blood in hyperlipidemia. In atherosclerosis, lipids deposit in the lining of the blood vessels, making the blood vessels harder, thicker, and less elastic.
Skip to 1 minute and 8 seconds Here, you can see the progression of atherosclerosis in a blood vessel, which normally begins from an initial lesion. With continued hyperlipidemia, there is an increased chance of the progression of a fatty streak, which is when lipids accumulate in the blood vessel wall. Ongoing hyperlipidemia can then result in small, fatty lumps that appear in blood vessels. Here we see atheroma formation, as indicated by the fats in yellow, starting to make the blood vessel narrower. As the buildup of fat continues, the disease worsens. This means that blood flow can become obstructed, and parts of the deposit, or the plaque, that forms in the blood vessel can break off and block a blood vessel elsewhere.
Skip to 2 minutes and 4 seconds Because of this, atherosclerosis can result in a number of serious conditions. In the early stages of atherosclerosis, the person will not have any noticeable symptoms. With time, however, the accumulation of the plaque can cause fibroatheromas and complicated lesions, which can impede blood flow. Also, plaques may rupture and lodge temporarily in smaller blood vessels to cause a number of conditions. Claudication is the result of a lack of blood flow to the legs, causing pain and limping, particularly when walking. Angina is a pain in the chest that occurs as a result of not enough blood, and therefore not enough oxygen, getting to the blood vessels within the heart lining. Not enough oxygen to tissues is called ischemia.
Skip to 3 minutes and 0 seconds A transient ischemic attack, or also called TIA, is caused by a temporary cut in the blood supply to the brain. A person that has a transient ischemic attack is at greater risk of having a heart attack or a stroke. If a plaque or a thrombus completely occlude the blood vessel, this may cause a heart attack when blood flow to the heart is blocked, or a stroke when blood flow to parts of the brain is blocked, and possibly death. To understand why atherosclerosis occurs, it is important to look at how lipids are transported around the body. Just about every cell in the body needs a supply of lipids for three main reasons.
Skip to 3 minutes and 48 seconds Lipids, including cholesterol, make up a large proportion of the cell’s outer layer, called the cell membrane. Secondly, many cells use lipids as a source of energy, and thirdly, some cells use lipids to make other products, such as hormones. Substances that dissolve in water travel freely in the blood. However, since lipids do not dissolve in water, they need a way to be transported around the blood. This occurs mostly via lipoproteins, which, as the name suggests, are a mixture of lipids and proteins. Lipoproteins get made in various parts of the body, and their role is to transport their contents to cells that need them. On the outer layer of the lipoprotein are lipids called phospholipids.
Skip to 4 minutes and 44 seconds Cholesterol locks into the outer layer and also in the middle of the lipoprotein and is transported around the body in this way, and so are another type of lipid called triglycerides. There are proteins on the surface of lipoproteins. These surface proteins are important, as cells have receptors that bind to these surface proteins. When this happens, the whole lipoprotein is engulfed by the cell, and the cell can then use the contents of the lipoprotein. There are three main types of lipoproteins that are named according to their density– very low density lipoproteins, low density lipoproteins, and high density lipoproteins, more commonly termed VLDL, LDL, and HDL.
Skip to 5 minutes and 35 seconds There is a fourth type called chylomicrons that are made in the small intestine and carry dietary lipids from the gut to the liver and to other tissues. These lipoproteins also vary in terms of the amount of cholesterol and triglycerides that they carry. VLDLs carry both triglycerides and cholesterol, but then they lose some of their triglycerides as they become LDLs in the blood. Thus LDLs have more cholesterol than VLDLs, and HDLs contain mostly cholesterol, and chylomicrons contain mostly triglycerides. So let’s look in more detail as to where those lipoproteins are made and what they do. Chylomicrons, as I said, are formed in cells in the small intestine and take mainly triglycerides and some cholesterol to tissues, including the liver.
Skip to 6 minutes and 33 seconds VLDLs are formed in the liver and are released into the bloodstream. When in the blood, some of the triglycerides that they carry are broken down so that they can be stored in fat cells or used as an energy source. This results in the formation of cholesterol rich lipoproteins called LDLs. The amount of LDL in plasma correlates with the risk of atherosclerosis, and an elevated level of LDL, which is sometimes called bad cholesterol, increases the risk of developing atherosclerosis.
Skip to 7 minutes and 16 seconds This is because under some conditions, LDLs can migrate into the blood vessel walls and cause the fatty accumulation and the plaques described previously. HDL are the smallest of the lipoproteins and function to take cholesterol from cells around the body back to the liver. They are made as discs in the liver and acquire cholesterol as they circulate. Thus, high levels of HDL are considered beneficial as they take cholesterol out of the general circulation. This is why HDL is termed good cholesterol. It is good to take cholesterol to the liver because cholesterol can be made into bile salts, and bile salts gets secreted into the small intestine in order to help with your digestion.
Skip to 8 minutes and 9 seconds While some of the bile salts are reabsorbed back into the bloodstream, some of the bile salts are excreted through the faeces. Thus, this is the only mechanism in which cholesterol can be excreted from the body. So the aim of treatments to decrease the risk of atherosclerosis centre around decreasing the levels of circulating cholesterol, thus decreasing the chance of atherosclerosis. Ideally, we want to decrease circulating LDLs by decreasing VLDLs since, as I said before, LDLs are formed from VLDLs that lose some of their triglycerides. Decreasing circulating LDLs can also be accomplished if the process of LDLs returning to the liver is promoted.
Skip to 9 minutes and 2 seconds As mentioned previously, lipoproteins have proteins on their surface that cells can recognise in the body. If the liver is running low on cholesterol, it can increase the expression of receptors that recognise specific proteins on LDLs. When this happens, more LDLs bind to receptors in the liver and are taken into the liver cells. Another aim of treatment is to increase circulating HDLs, as HDLs are the lipoproteins that acquire cholesterol from cells and take it back to the liver. So in this section, you learned what hyperlipidemia and atherosclerosis are and why hyperlipidemia is a risk factor in the development of atherosclerosis, which, if left unchecked can lead to serious conditions such as heart attack and stroke.
Skip to 9 minutes and 55 seconds You’ve seen how lipids are transported around the body and how the aim of treatments that decrease the risk of atherosclerosis centre around modifying circulating lipids.
Heart disease: physiology
Watch Dan explain how lipids are transported around the body, what atherosclerosis is and why atherosclerosis increases the risk of diseases such as heart disease.
As you make your way through the course, you may like to return to this video and replay particular sections to review Dan’s presentation on heart disease physiology.
© Monash University 2020. CRICOS No. 00008C