Lecture 9 - Atherosclerosis and Dyslipidemias

Question 1

lipid transport throughout the body is mediated by ____

Answer 1

lipoprotein complexes

Question 2

what are the three major types of lipoprotein complexes examined in this course?

Answer 2

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

Question 3

packages of lipids (triglycerides, cholesterol) surrounded by apolipoproteins and phospholipids

Answer 3

lipoproteins

Question 4

lipoproteins are categorizes according to ____

Answer 4

size and prescence of specific apolipoproteins

Question 5

what is an atherosclerotic plaque?

Answer 5

fatty deposits that occlude blood vessels, they form over time as cholesterol accumulates in the plaque

Question 6

accumulation of cholesterol occurs over time in ____ that have invaded the ____ of a blood vessel

Answer 6

transformed macrophages (foam cells), endothelial wall

Question 7

macrophages have mechanisms for uptake of LDL and VLDL via the ____, leading to cholesterol ____

Answer 7

LDL receptor and ApoE receptor, accumulation

Question 8

mechanisms for cholesterol efflux in macrophages is mediated by ____

Answer 8

HDL (good cholesterol)

Question 9

what is the overall approach of therapies for atherosclerosis?

Answer 9

to reduce circulating LDL-C

Question 10

blood vessels are protected by a thin, fibrous cap. thinning of the cap exposes _____ that can lead to _____ and _____.

Answer 10

pro-thrombotic factors, thrombi (clots), total vessel occlusion

Question 11

the primary treatment for atherosclerosis (reduction of thrombotic clots and LDL-C)

Answer 11

statins

Question 12

VLDL and LDL formation is primarily regulated in the ____

Answer 12

liver

Question 13

cholesterol that is packaged in the liver can be dietary/extrinsic, OR ____

Answer 13

synthesized in the liver hepatocyte

Question 14

how are dietary/extrinsic cholesterols brought into liver hepatocytes?

Answer 14

taken up via the LDL receptor

Question 15

the pathway for cholesterol synthesis in the liver

Answer 15

mevalonate pathway

Question 16

the rate-limiting enzyme in the mevalonate pathway which is targeted by statins

Answer 16

HMG-CoA reductase

Question 17

catalyzes that formation of mevalonic acid from HMG-CoA

Answer 17

HMG-CoA reductase

Question 18

where is HMG-CoA found?

Answer 18

the ER membrane

Question 19

what are the direct effects of inhibiting HMG-CoA reductase?

Answer 19

• reduction of cholesterol pool in hepatocytes
• increased expression of LDL receptors on hepatocytes
• more LDL is scavenged from the blood

Question 20

competitive inhibitors of HMG-CoA reductase

Answer 20

statins

Question 21

atorvastatin (commercial name lipitor)

Answer 21

a prodrug which must be processes by first-pass metabolism in the liver, converted form is a competitive inhibitor of HMG-CoA reductase

Question 22

lovastatin

Answer 22

a prodrug and a statin, converted form is a competitive inhibitor of HMG-CoA reductase

Question 23

is it a bad thing for statins to be administered as prodrugs?

Answer 23

no since their primary target organ is the liver anyways

Question 24

a class of drugs used to treat dislipidemias

Answer 24

fibrates

Question 25

fenofibrate

Answer 25

a type of fibrate which targets the peroxisome proliferator-activated receptors

Question 26

this family of receptors are intracellular receptors that act as transcription factors and influence transcrition of target genes

Answer 26

peroxisome proliferator-activated receptors (PPARs)

Question 27

are fibrates agonists or antagonists of PPARs

Answer 27

agonists

Question 28

what are the important outcomes of using fibrates?

Answer 28

• increased expression of lipoprotein lipase
• increased breakdown of triglycerides in VLDLs
• increased uptake of fatty acids as fuel in peripheral tissues
• increased LDL uptake in the liver
• reduced VLDL production in the liver

Question 29

which is more effective: statins or fibrates?

Answer 29

statins