Lecture 9 - ATHEROSCLEROSIS AND DYSLIPIDEMIAS

Question 1

Lipid transport throughout the body is mediated by 3 lipoprotein complexes:

Answer 1

• HDL (high density lipoprotein)
• LDL (low density lipoprotein)
• VLDL (very low density lipoprotein
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Question 2

Lipids are ____ in blood or water; they travel around the lipoproteins.

Answer 2

not soluble

Question 3

High level of total ____ are linked to adverse cardiovascular events which is attributed to the formation of atheroscleorotic plaques.

Answer 3

cholesterol

Question 4

What is the leading cause of death in North America?

Answer 4

Rupture of atherosclerotic plaques followed by occlusion of vessels in the heart or brain

Question 5

What is Artherosclerosis?

Answer 5

Fatty deposits that occlude blood vessels and form plaques overtime as cholesterol accumulates.

Question 6

Accumulation of cholesterol occurs over time in transformed macrophages also known as ____ cells that have invaded the ________ of a blood vessel.

Answer 6

FOAM; endothelial wall

Question 7

• Is high LDL a good thing?
• Is high HDL a good thing?

Answer 7

• High LDL is a bad thing as it means that you are delivering/adding more cholesterol to plaques
• High HDL is a good thing as it means you are taking cholesterol away from the plaque.

Question 8

What prodrugs are effective in controlling cholesterol content in the body?

Answer 8

Statins

Question 9

Where is VLDL and LDL regulated in the body?

Answer 9

regulated in the liver.

Question 10

Where is cholesterol formed?

Answer 10

liver

Question 11

LDL circulating around the body can be taken up by ____ cells and by ____ cells by LDL receptors.

Answer 11

peripheral;liver

Question 12

Cholesterol that is packaged can be dietary/____ (taken up via the ____ receptor) or synthesized in the ____ ____

Answer 12

extrinsic; LDL; liver hepatocyte.

Question 13

What key enzyme is involved in the formation of cholesterol?

Answer 13

HMG-CoA reductase

Question 14

What is the effect on cholesterol if HMG-CoA reductase is inhibited?

Answer 14

reduction in the amount of cholesterol produced by the liver; leads to an increased expression of LDL receptors on the hepatocyte.

Question 15

HMG-CoA is a ____ protein, primarily residing in the ER membrane.

Answer 15

transmembrane

Question 16

HMG-CoA leads to the formation of an intermediate known as ____ acid from its precursor, HMG-CoA.

Answer 16

Mevalonic

Question 17

____ are competitive inhibitors of HMG-CoA reductase

Answer 17

Statins.

Question 18

Cellular response of statins is to generate more ____ receptors to scavage ____/cholesterol from the bloodstream.

Answer 18

LDL;LDL

Question 19

What is a common statin, competitive inhibitor of HMG-CoA reductase?

Answer 19

Atorvastatin

Question 20

Statins are ____ extraction drugs that are rapidly absorbed and processed by first pass metabolism.

Answer 20

high

Question 21

Does cholesterol synthesis take place during sleep or when you are awake?

Answer 21

during sleep

Question 22

____ are agonists of PPArs, peroxisome proliferator-activated receptor (intracellular receptors)

Answer 22

Fibrates

Question 23

Fibrates is used to treat what?

Answer 23

dyslipidemias

Question 24

PPARs bind to their ligand –> receptors ____ with RXR (retinoic acid receptors) —> increase expression of ____ lipase.

Answer 24

dimerize; lipoprotein

Question 25

Increased expression of lipoprotein lipase leads to ____ breakdown of triglycerides in ____ receptors and uptake of fatty acids as fuel in peripheral tissues.

Answer 25

increased; VLDL