AstraZeneca has delivered this text only version of the course to serve those users who have difficulty accessing the interactive version.
You can access it here: Demo Interactive Version
Further information can be found at: "Dyslipidaemia and Atherosclerosis" main page
More tutorials at: eCME Homepage
Welcome to "Dyslipidaemia".
Before beginning, please take a moment to read the course details.
Course Length: Approximately 2 hours.Your
time may vary based on modem speed, prerequisite knowledge and
other factors.
Prerequisites: Anatomy and Physiology of the
Cardiovascular System.
Date Published: March 2003
Valid Until: March, 2006
This course, Dyslipidaemia, should serve as a foundation for learning about therapies to treat and prevent atherosclerosis and should also help you interact more effectively with health care professionals who treat patients with dyslipidaemias and atherosclerosis. It is divided into five sections.
The first section, AETIOLOGY, introduces the different types of lipids and lipoproteins, describes the normal metabolism of lipids, and the mechanisms that lead to dyslipidaemia.
The second section, EPIDEMIOLOGY, reviews the human and experimental studies that have linked dyslipidaemia to cardiovascular disease and the risk factors that have been identified.
The third section, PROGNOSIS, explains how dyslipidaemia contributes to atherosclerosis and how this manifests itself in cardiovascular diseases such as stroke, and angina. This section explains how plaques are formed.
The fourth section, DIAGNOSIS, explains how dyslipidaemia is assessed and how the risk of cardiovascular disease is predicted from these analyses. Clinical evaluation of disease is also covered in this section.
The fifth section, TREATMENT, covers the dietary and lifestyle changes that can affect atherosclerosis and the types of pharmacological therapies that are currently used. In particular, the mechanism of action and use of statins is covered in detail.
This section introduces lipids and lipoproteins, their normal metabolism, and the disorders of lipoprotein metabolism that are associated with atherosclerosis.
These are the objectives for this section.
After you finish this section, you should be able to:
Lipids are fat or fat-like substances, which are insoluble in water. They are important dietary constituents with many functions, but they are primarily used by the body as a major source of energy. They include simple lipids (cholesterol and fatty acids,) as well as complex lipids (cholesterol esters and glycerol esters, i.e. triglycerides). This lesson introduces you to the structures and roles of lipids.
Lipids, or fats, are essential for life. They:
The lipids can be simple lipids or complex lipids. Cholesterol is an example of a simple lipid.
It is a steroid alcohol consisting of a four-ringed steroid nucleus together with a hydroxyl group. It can exist either as a free sterol, as in cell membranes, or as an ester combined with a long-chain fatty acid, as in the plasma. It is a component of cell membranes and essential for the synthesis of bile salts, vitamin D and hormones.
Fatty acids are organic acids containing carbon, hydrogen and oxygen. They are the basic building blocks of most simple lipids. Most are synthesised in the body, although some must be obtained from the diet. Fatty acids exist in three forms, saturated, monounsaturated and polyunsaturated, which are distinguished according to the number of double bonds between the hydrocarbon chain and carbon atoms. Complex lipids are produced when cholesterol or fatty acids combine with molecules, which contain alcohol, such as glycerol, to form compounds known as esters. There are three main types.
Triglycerides are produced by the esterification of glycerol with three fatty acid molecules. They are stored mainly in adipose tissue and provide an alternative source of energy, by the release of fatty acids, when the body's carbohydrate energy reserves are very low.
Phospholipids are glycerol esters containing two fatty acids. They have a water-soluble and a lipid-soluble surface and are an important component of cell membranes.
In the blood, cholesterol is mainly found in the esterified form. Cholesterol esters are the stored form of cholesterol in cells.
Cholesterol and triglycerides are insoluble in water and therefore have to be modified before they can be transported in the bloodstream. This is achieved by combining lipids with proteins known as apolipoproteins, to form carrier complexes called lipoproteins. This lesson introduces you to the structures and roles of lipoproteins.
As lipids are insoluble in water, they are transported through the bloodstream in chemical complexes called lipoproteins. Lipoproteins are tiny spheres with a core of varying amounts of hydrophobic, esterified cholesterol, and triglycerides wrapped in a shell composed mainly of phospholipids.
Phospholipids are polar molecules, with one hydrophobic end pointing into the lipid core and the other hydrophilic or water-soluble end facing out into the "watery" blood plasma. The outer layer also contains apolipoproteins. These proteins stabilise the structure and act as 'labels' for the different types of lipoprotein, enabling receptors on the cells that metabolise them to recognise and bind the lipoprotein.
Lipoproteins may be classified into six types according to their density, size, and composition. Each type varies in lipid and protein composition and serves a different role in transporting lipids from sites of synthesis and absorption to sites of utilisation. This is summarised in the table shown here.
Cholesterol is one of the most important lipids, so we will look at its synthesis and metabolism in detail. The body synthesises most of the cholesterol it uses in the liver and, to a lesser extent, in the walls of the small intestine. This lesson describes the cholesterol biosynthetic pathway.
The liver combines molecules of acetyl coenzyme A or acetyl CoA to synthesise cholesterol. The steps in this biosynthetic pathway are shown here and include the following intermediates: acetoacetyl CoA, 3-hydroxyl-3-methylglutaryl CoA or HMG CoA, Mevalonate, Squalene and Lanosterol.