Cardio

Question 1

What do HDL particles contain?

Answer 1

contain apoA1 and apoA2

Question 2

What do LDL particles contain?

Answer 2

contain apoB-100

Question 3

What do VLDL particles contain?

Answer 3

contain apoB-100

Question 4

What do chylomicrons contain?

Answer 4

contain apoB-48

Question 5

Summarise the life cycle of ApoB containing liposomes?

Answer 5

Assembly [with apoB100 in the liver and apoB48 (a truncated variant) in the intestine]

Intravascular metabolism (involving hydrolysis of the triglyceride core)

Receptor mediated clearance

Question 6

Which protein is responsible for the uptake of cholesterol?

Answer 6

Niemann-Pick C1 like protein

Question 7

What activates chylomicrons and VLDL?

Answer 7

Transfer of apoCII from HDL

Question 8

Where is LPL found?

Answer 8

associated with the endothelium of capillaries

Question 9

What apoCII do?

Answer 9

facilitates binding on chylomicron and VLDL to LPL

Question 10

What does LPL do?

Answer 10

Hydrolyses core triglycerides to free fatty acids and glycerol which enter tissues

Question 11

How is LDL cleared?

Answer 11

Cellular uptake of LDL particles occurs via receptor-mediated endocytosis

Within the cell at the lysosome, cholesterol (C) is released from cholesteryl ester (CE) by hydrolysis

Released cholesterol causes:
inhibition of HMG-CoA reductase which is the rate limiting enzyme in de novo cholesterol synthesis
down regulation of LDL receptor expression
storage of cholesterol as cholesterol ester

Question 12

Why is LDL bad cholesterol

Answer 12

oxidised to athrogenic OXLDL

Migration of monocytes (white blood cell) across the endothelium into the intima where they become macrophages

Uptake of OXLDL by macrophages (using scavenger receptors) converts them to cholesterol-laden foam cells that form a fatty streak (an early event in atherogenesis)

Release of inflammatory substances from various cell types causes division and proliferation of smooth muscle cells into the intima and the deposition of collagen

The formation of an atheromatous plaque consisting of a lipid core (product of dead foam cells) and a fibrous cap (smooth muscle cells and connective tissue)

Question 13

Why is HDL the ‘Good’ Cholesterol?

Answer 13

accepts excess cholesterol from the plasma membrane of cells (e.g. macrophages) and delivers cholesterol to the liver, known as reverse cholesterol transport, by several mechanisms;
>HDL reaching the liver interacts with a receptor (scavenger receptor-B1, SR-B1) that allows transfer of cholesterol and cholesteryl esters into hepatocytes
>In the plasma, cholesterol ester transfer protein (CETP) mediates transfer of cholesteryl esters from HDL to VLDL and LDL, indirectly returning cholesterol to the liver

Question 14

What is the drug treatment for elevated LDL?

Answer 14

Statin and ezetimibe

Question 15

What is the drug treatment for elevated LDL and VLDL?

Answer 15

Fibrates, statin, nicotinic acid

Question 16

What is the drug treatment for elevated BVLDL?

Answer 16

Fibrates

Question 17

What is the drug treatment for elevated VLDL?

Answer 17

Fibrates

Question 18

What is the drug treatment for elevated Chylomicrons and VLDL?

Answer 18

Fibrate, niacin, fish oil and statin combination

Question 19

Describe the action of statins?

Answer 19

competitive inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase - rate limiting step in cholesterol synthesis in hepatocytes

Decrease in hepatocyte cholesterol synthesis causes a compensatory increase in LDL receptor expression and enhanced clearance of LDL (note: statins are ineffective in homozygous familial hypercholesterolaemia where LDL receptors are lacking

Question 20

Other beneficial effects of statins?

Answer 20

Decreased inflammation
Reversal of endothelial dysfunction
Decreased thrombosis
Stabilization of atherosclerotic plaques

Question 21

How are statins administered?

Answer 21

Administered orally at night

Question 22

Adverse effects of statins?

Answer 22

include myositis and rarely rhabdomyolosis incidence of which is increased if statin is combined with a fibrate

Question 23

How do fibrates work?

Answer 23

First line drugs in patients with very high triglyceride levels

agonists of a nuclear receptor (PPARa) to enhance the transcription of several genes, including that encoding LPL

Question 24

Which drugs inhibit cholesterol synthesis?

Answer 24

Bile acid binding resins (colestyramine, colestipol, colsevelam) cause the excretion of bile salts resulting in more cholesterol to be converted to bile salts by interrupting enterohepatic recycling

Question 25

How are bile acid binding resins absorbed?

Answer 25

not absorbed from GI tract

Question 26

How does ezetimbe work?

Answer 26

Relative new agent, acts to inhibit Niemann-Pick C1 like-1 (NPC1L1) transport protein in enterocytes of the duodenum, reducing the absorption of cholesterol

Question 27

When is ezetimbe used?

Answer 27

in combination with statins when the latter alone does not achieve a sufficient response