Familial Hypercholesterolemia

Question 1

CardioVascular Disease

Answer 1

Cardiovascular or heart disease is a class of disease that involves the heart or blood vessels (arteries, capillaries and veins). The most common type of heart disease,

Question 2

Atherosclerosis

Answer 2

Caused by plaque building up along the inner walls of the arteries, which narrows the arteries and restricts blood flow.

Question 3

Atherosclerotic plaques

Answer 3

Contain proteins, lipids and cholesterol

Question 4

Cholesterol and function

Answer 4

Waxy and hydrophobic;
Integral part of cell membrane;
Precursor for hormones
Precursor for Vitamin D
Precursor for Bile acids

Question 5

Cholesterol ester

Answer 5

Transfer form of Cholesterol

Question 6

Sources of Cholesterol

Answer 6

Dietary cholesterol
Synthesis of cholesterol

Question 7

Cholesterol synthesis pathway

Answer 7

HMGCoA reductase facilitates LDL synthesis

Question 8

LDL

Answer 8

Low Density Lipoprotein

Question 9

VLDL

Answer 9

Very Low Density Lipoprotein

Question 10

HDL

Answer 10

High Density Lipoprotein

Question 11

IDL

Answer 11

Intermediate Density Lipoprotein

Question 12

What is the pathophysiology of FH?

Answer 12

Lack of LDL receptor expressed by hepatic cells in homozygotes
Reduced amount of LDL receptors
expressed by hepatic cells in heterozygotes

Question 13

The MoA of Statin?

Answer 13

If there is less LDL in the hepatic cells, cells will upregulate LDL receptors to take up more LDLs
Statin blocks the HMGCoA reductase which will decrease the Cholesterol synthesis –> low LDL levels in the liver –> Liver upregulate LDL receptors –> Takes up more LDL from the bloodstream

Question 14

HMGCoA reductase

Answer 14

HMG-CoA reductase is an enzyme found in the liver that plays a key role in the synthesis of cholesterol. It is responsible for converting HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) to mevalonic acid, which is a key intermediate in the biosynthesis of cholesterol and other important molecules such as CoQ10.

HMG-CoA reductase is the target of a class of drugs called statins, which are commonly used to lower cholesterol levels in people with high blood cholesterol levels. Statins work by inhibiting the activity of HMG-CoA reductase, which reduces the amount of cholesterol that is produced in the liver.

Question 15

Adjusting the diet to eliminate the intake of dietary cholesterol can decrease the circulating cholesterol levels, but often has only minor effects. Explain why a no cholesterol diet can have such limited effects.

Answer 15

Cholesterol is an essential component of membranes, needed by all cells. If little or no cholesterol is being consumed, the cells of the liver (and other cells) will increase synthesis so that there is sufficient cholesterol available to all cells

Question 16

Bile Acids

Answer 16

Bile acids are a group of steroid acids that are synthesized in the liver and secreted into the small intestine to aid in the digestion and absorption of fats. They are derived from cholesterol and are important for the solubilization and absorption of dietary lipids, including cholesterol, fatty acids, and fat-soluble vitamins such as A, D, E, and K.

Bile acids also play a role in the regulation of cholesterol metabolism, as they stimulate the synthesis of bile salts in the liver and inhibit the synthesis of cholesterol. Additionally, they are involved in the absorption and metabolism of drugs and other xenobiotics.

Question 17

PCSK9 gene

Answer 17

Causes the degradation of the LDL receptors
The PCSK9 (Proprotein Convertase Subtilisin/Kexin type 9) gene is a gene that encodes a protein involved in the regulation of cholesterol metabolism. The PCSK9 protein is produced primarily in the liver and plays a key role in the regulation of low-density lipoprotein (LDL) cholesterol levels in the bloodstream.

PCSK9 protein binds to the LDL receptor on the surface of liver cells and promotes its degradation, which results in reduced clearance of LDL cholesterol from the bloodstream. This leads to increased levels of LDL cholesterol in the blood, which is a major risk factor for cardiovascular disease.

Question 18

The MoA of Statin?

Answer 18

If there is less LDL in the hepatic cells, cells will upregulate LDL receptors to take up more LDLs
Statin blocks the HMGCoA reductase which will decrease the Cholesterol synthesis –> low LDL levels in the liver –> Liver upregulate LDL receptors –> Takes up more LDL from the bloodstream
(remember the distinctions of LDL in the liver and the bloodstream, we want less LDLs in the bloodstream and more LDLs in the liver for the liver to metabolized them)