Lecture 25

Question 1

Where does cholesterol in the body come from?

Answer 1

Diet and is synthesized in the liver.

Question 2

Cholesterol biosynthesis happens where in the body?

Answer 2

Liver

Question 3

These are spherical structures with an outer wall made of phospholipids, cholesterol, and proteins (apolipoproteins) that carry cholesterol and triglycerides (TAG) within the body.

Answer 3

Lipoproteins

Question 4

Transports dietary cholesterol and triglycerides to various tissues in body

Answer 4

Chylomicrons

Question 5

Transports mostly triglycerides from liver to adipose tissue

Answer 5

VLDL (very low density lipoprotein)

Question 6

Remnant of VLDL after it delivers triglycerides to tissue; May be cleared from the blood via direct uptake by the liver or remodeled into LDL

Answer 6

IDL (intermediate density lipoprotein) also called VLDL remnant

Question 7

• Transports mostly cholesterol from liver to various tissues of body
• Removed from circulation via LDL receptors in the liver

Answer 7

LDL (low density lipoprotein)

Question 8

i. Transports cholesterol from peripheral tissues back to liver where it can be excreted via bile

Answer 8

HDL (High density lipoprotein)

Question 9

This type of lipoprotein is antiatherogenic

Answer 9

HDL (High density lipoprotein)

Question 10

Has:

• antiinflammatory properties
• antioxidant properties
• inhibits LDL oxidation
• inhibits monocyte migration into subendothelial space
• Prothrombic properties

Answer 10

Antiatherogenic

Question 11

Unhealthy blood cholesterol levels, high BP, smoking, insulin resistance, diabetes, hyperglycemia, obesity and physical inactivity are risk factors for what disease?

Answer 11

Atherosclerosis

Question 12

This is the space between the basement membrane and the internal elastic lamina where fatty streaks develop

Answer 12

Subendothelial space

Question 13

This type of injury allows LDL to infiltrate into subendothelial space of the artery

Answer 13

Endothelial artery

Question 14

Oxidized LDL (oxLDL) in subendothelial space and altered expression (increase) of adhesion molecules on vessel wall due to endothelial injury cause this to happen.

Answer 14

Migration of monocytes and T-cells

Question 15

When monocytes migrate into subendothelial space, they differentiate into _________ with scavenger receptors.

Answer 15

Macrophages

Question 16

Macrophages endocytose ______ in the subendothelial space

Answer 16

oxLDL

Question 17

Foam cell formation and formation of fatty streaks in subendothelial space are casued by what?

Answer 17

oxLDL endocytosis by macrophages

Question 18

Release of _____ by foam cells and T cells in subendothelial space cause:

• smooth muscle migration and proliferation (rapid reproduction)
• formation of fibrous cap
• preceipitation of calcium

Answer 18

Cytokines

Question 19

Once calcium preciptates into the subendothelial space, this is formed in the artery.

Answer 19

Hard plaque

Question 20

Plaque rupture can lead to ___ formation

Answer 20

Clot

Question 21

This is when a vessel ruptures due to the weakening of vessel wall leads to dilation or “ballooning”

Answer 21

Aneurysm

Question 22

This is turbulent blood flow in regions o curvature or bifurcation which can cause endothelial damage

Answer 22

Shear stress

Question 23

Smoking causes carbon monoxide injury to endothelium and _____ rate of LDL oxidation.

Answer 23

Increased

Question 24

Causes of endothelial injury

Answer 24

Shear stress, hypertension, smoking

Question 25

True or False? When LDL concentration is higher, the LDL molecule circulates longer before it is removed.

Answer 25

True

Question 26

The longer the LDL circulates, the the fraction of LDL that will enter the wall and become oxidized increases or decreases?

Answer 26

Increases

Question 27

This growth factor normally functions to protect vessels against injury

Answer 27

TGF-beta

Question 28

Does LDL enhance or suppress the activity of TGF beta?

Answer 28

Suppress

Question 29

1. Increases vascular smooth muscle cell proliferation 2. Increases macrophage engulfment of oxLDL 3. Decreases endothelial nitric oxide production 4. Increases the production of advanced glycation end-products (AGEs).

Answer 29

Role of hyperglycemia in atherosclerosis

Question 30

An ___ is a result of a chain of chemical reactions after an initial non-enzymatic glycation (sugar attachment) of a protein or lipid; this changes the structure and function of proteins and lipids

Answer 30

AGE - advanced glycation end-product

Question 31

-Promote cross-linking of proteins in arterial wall leading to trapping of oxLDL molecules

Answer 31

AGE

Question 32

-Alters ECM (extracellular matrix) proteins leading to a decrease in vascular compliance

Answer 32

AGE

Question 33

-Generate ROS (enhance neutrophil respiratory burst)

Answer 33

AGE

Question 34

-Stimulate inflammatory and pro-thrombotic signaling in endothelial cells, macrophages, and vascular smooth muscle cells

Answer 34

AGE

Question 35

Pharmacological therapy for atherosclerosis involving HMG CoA Reductase inhibitors

Answer 35

Statins

Question 36

Pharmacological therapy for atherosclerosis that a. lowers LDL by blocking intestinal absorption of cholesterol

Answer 36

Cholesterol absorption inhibitors

Question 37

Pharmacological therapy for atherosclerosis that decreases VLDL secretion by liver which lowers LDL and decreases catabolism of HDL leading to elevated levels of HDL

Answer 37

Niacin

Question 38

Pharmacological therapy for atherosclerosis that increases clearance of triglyceride rich lipoproteins (VLDL, chylomicrons) and increases HDL

Answer 38

Fibric acid derivatives

Question 39

Pharmacological therapy for atherosclerosis by lowering LDL by binding bile acids in GI tract leading to increased elimination in stool which forces liver to use cholesterol to synthesize more bile acids. Also, Increases LDL receptor expression in liver which enhances removal of LDL from circulation

Answer 39

Bile acid sequestrants