Lecture 20: Atherosclerosis

Question 0

What is atherosclerosis?

Answer 0

A disease affecting innermost layer of large and medium sized arteries

Question 1

How many deaths does atherosclerosis contribute in the western world?

Answer 1

> 50%

Question 2

What does atherosclerosis appear as?

Answer 2

Thickenings called plaques

Question 3

What are plaques?

Answer 3

Deposits of fibrous tissues and lipids

Question 4

What is the difference between arteriosclerosis and atherosclerosis ?

Answer 4

Arteriosclerosis is the general term for hardening of arteries

Atherosclerosis is a type of arteriosclerosis

Question 5

What does atherosclerosis affect?

Answer 5

Arteries

Question 6

How many layers does an arterial wall consist of?

Answer 6

Three layers

Question 7

What is the inner most layer called?

Answer 7

Tunica intima

Question 8

What is the middle layer called?

Answer 8

Tunica media

Question 9

What is the outer layer called?

Answer 9

Tunica adventitia

Question 10

Where do the plaques causing atherosclerosis form?

Answer 10

In the tunica intima

Question 11

What makes up the tunica intima?

Answer 11

Tunica intima consists of Endothelial cells lying on a basement membrane

Question 12

What are endothelial cells?

Answer 12

Flattened cells separated by tight junctions

Question 13

What is the function of endothelial cells?

Answer 13

Many functions
Containment of blood
Selective transport of fluids, gases, ions and proteins into tissues
Control of clotting
Control of blood pressure

Question 14

What does the tunica media consist of?

Answer 14

Two layers of elastic laminae with vascular smooth muscle cells in between them

Question 15

What are vascular smooth muscle cells?

Answer 15

Fascinating cells which contract to regulate vessel diameter

And regulate function and fate of other cells in the vessel wall by secreting cytokines and growth factors

They also lay down extracellular matrix.

Question 16

What does the tunica adventitia consist of.

Answer 16

Connective tissue

Question 17

Why do different cell types within vessel walls have to continually communicate

Answer 17

So they can regulate one another’s state and function

Question 18

What does the exact structure of arteries depend on?

Answer 18

Their size.

Large arteries like aorta and carotid are exposed to high pulsatile pressures so they have prominent elastic laminae hence called elastic arteries

Medium sized arteries like coronary arteries are classified as muscular arteries as their media is composed largely of smooth muscle cells.

Question 19

What are the four major positive risk factors for atherosclerosis?

Answer 19

Hyperlipidaemia
Cigarette smoking
Hypertension
Diabetes mellitus

Question 20

What are the other additional positive risk factors for atherosclerosis?

Answer 20

Advancing age
Family history
Make gender 
High saturated fat diet
Stressful sedentary lifestyles
Obesity
Excess alcohol consumption
Low birth weight
Low socioeconomic status
Infections - chlamydia organisms

Question 21

What are the three main negative risk factors of atherosclerosis ?

Answer 21

High levels of circulating HDLP (high density lipoproteins)
Moderate alcohol consumption (2 units per day)
Cardiovascular fitness

Question 22

Why are lipoproteins important?

Answer 22

They are powerful risk modifiers for atherosclerosis

Question 23

What are lipoproteins?

Answer 23

They consist of a lipid core (e.g. Triglycerides, cholesterol, cholesterol esters, phospholipids) surrounded by a protein coat

Question 24

What are the proteins in the protein coat of lipoproteins called?

Answer 24

Apolipoproteins

Question 25

Why are lipoproteins risk modifiers?

Answer 25

High density lipoproteins are the good type of cholesterol that take lipids away from the liver, therefore they lower the risk of atherosclerosis

Question 26

What does the initiation of atherosclerosis involve?

Answer 26

Endothelial cell knjury

Question 27

What is the progression of atherosclerosis following initial EC injury an example of?

Answer 27

Chronic inflammation

Question 28

Outline the pathogenesis of atherosclerosis?

Answer 28

Endothelial cell injury Leukocyte migration Smooth muscle cell activation and migration Lipoprotein filtration

Question 29

What is atherogenesis?

Answer 29

The pathogenesis of atherosclerosis

Question 30

What can endothelial cell injury be caused by?

Answer 30

A combination of Haemodynamic force of blood (hypertension, branch points) Chemical insults (cigarette smoke, lipids) Cytokines

Question 31

What can damage of endothelial cells lead to?

Answer 31

Altered permeability, > lipid infiltration Adhesion of leukocytes (due to enhanced expression of chemokines and adhesion molecules) Activation of thrombosis

Question 32

What is leukocyte migration into the anterosclerotic plague a type of?

Answer 32

Chronic inflammation which is a hallmark of atherosclerosis

Question 33

What do circulating monocytes on other leukocyte types adhere to? And what do they enter?

Answer 33

Endothelial cells. They enter the atherosclerotic leison

Question 34

What happens when circulating monocytes and other leukocyte types enter the atherosclerotic leison?

Answer 34

They ingest large amounts of oxidised lipoproteins This gives them a foamy appearance They are called foam cells

Question 35

What other cells also play an important role?

Answer 35

T lymphocytes and dendritic cells

Question 36

Recently, what have neutrophils and mast cells been for to perform?

Answer 36

Important functions during atherogenesis

Question 37

Which cells produce growth factors that activate vascular smooth muscle cells?

Answer 37

Macrophages, platelets, and endothelial cells

Question 38

What do smooth muscle cells do once activated by growth factors?

Answer 38

Proliferate and migrate from tunica media to the tunica intima

Question 39

What is the migration of smooth muscle cells into the tunica intima likely to be caused by?

Answer 39

Damage or incomplete development of internal elastic lamina. But this is not certain

Question 40

What other roles do smooth muscle cells play in atherosclerotic plaques?

Answer 40

They lay down extracellular matrix which contributes to a fibrous cap This may later be degraded by matrix degrading protease enzymes Vascular smooth muscle cells also ingest lipids, and interact with other cell types in the plaque through adhesion molecules present on their surface and growth factors which they secrete.

Question 41

What happens to lipoproteins in plaques?

Answer 41

They become oxidised

Question 42

What do oxidised lipoproteins attract?

Answer 42

Monocytes and stimulate several cell types in the plaque to release cytokines and growth factors,

Question 43

What do the oxidised lipoproteins cause?

Answer 43

Dysfunction and apoptosis in smooth muscle cells, macrophages and endothelial cells

Question 44

What do these changes (EC cell injury, leukocyte migration, smooth muscle cell activation and migration, lipoprotein infiltration) together result in ?

Answer 44

A spectrum of leisons

Question 45

Which leisons are clinically silent?

Answer 45

Type I initial lesion in isolated macrophage foam cells Type II fatty streak lesion mainly due to intracellular lipid accumulation Type III intermediate lesion due to type II changes and small extracellular lipid pools

Question 46

What are the clinically silent or overt lesions?

Answer 46

Type Iv atheroma lesion due to type II changes and core of extracellular lipid Type V fibroatheroma lesion due to lipid core and fibrotic layer or multiple lipid cores and fibrotic layers, or mainly calcific or mainly fibrotic Type VI complicated lesion due to surface defect, hematoma-haemorrhage, thrombus

Question 47

What are the types of lesions in sequence progression?

Answer 47

Type I initial lesion Type II fatty streak lesion Type III intermediate lesion Type IV atheroma lesion (can lead straight to type VI complicated leison) Type V fibroatheroma lesion Type VI complicated lesion

Question 48

What do lesion type I, II, III and IV have in common?

Answer 48

They are all grown mainly by lipid accumulation

Question 49

What is type V lesion's main growth mechanism?

Answer 49

accelerated smooth muscle and collagen increase

Question 50

What is type VI lesion's main growth mechanism?

Answer 50

Thrombosis, hematoma

Question 51

Which types of lesions occur from first decade?

Answer 51

Type I and type II

Question 52

Which types of lesions occur from third decade?

Answer 52

Type III and type Iv

Question 53

What types of lesions occur from the fourth decade?

Answer 53

Type V and type VI

Question 54

What does the fibrous cap of an atheroma lesion consist of?

Answer 54

Smooth muscle cells, macrophages, foam cells, lymphocytes, collagen, elastin, proteoglycans, neovascularisation

Question 55

What does the necrotic centre of an atheroma lesion contain?

Answer 55

Cell debridement cholesterol crystal sum foam cell am calcium

Question 56

What are the consequences of atherosclerosis?

Answer 56

Atheroma often silent due to pre-clinical phase until sudden onset of symptoms (due to rupture haemorrhage or thrombosis) Common clinical consequences of atherosclerosis: Myocardial infarction, peripheral vascular disease, and cerebrovascular disease