Atherosclerosis

Question 1

Atherosclerosis

Answer 1

Disease affecting the innermost layer of large and medium sized arteries. Appears as focal thickenings called ‘plaques’, which are deposits of fibrous tissues and lipids.

Thought to contribute to 50% of deaths in the western world

Question 2

What layer of the endothelium wall is affected in atherosclerosis

Answer 2

The Tunica intima.
Contains
-endothelial cells(in contract w intra-vascular cells): involved in BP and inflammation, separated by tight junctions,

• Scattered myointimal cells
• BM: presents growth factors, anchors cells, with a IEL

Question 3

Tunica Media of arteries

Answer 3

an EEL and smooth muscle cells

SM: regulates flow by contraction, and stabilise EC by secreting ECM and activating TGF-beta

Question 4

What do the Elastic Lamina Layers look like in a histology section?

Answer 4

Pink and wavy

Question 5

Tunica Adventitia of the arteries

Answer 5

Connective Tissue: fibroblasts, nerves, leucocytes, lymphatics, blood vessels (vasovasora)

Question 6

How is the exact structure of arteries dependent on their size?

Answer 6

Large arteries > exposed to high-pulsitile pressures > have prominent elastic laminae and are called “elastic arteries”

Medium Sized arteries > media largely composed of SM cells > “muscular arteries

Question 7

Muscular arteries

Answer 7

eg) coronary arteries
- Media largely composed of SM fibres
- Few elastic fibres
- Separate Int/Ext elastic Laminae

Question 8

Large elastic arteries

Answer 8

eg) Aorta, common carotid
- Media contains prominent elastic laminae
- Int/Ext Elastic laminae continuous
- Exposed to high pulsitile pressure
- Elastic recoil assist w continuous flow

Question 9

Arterioles

Answer 9

Small branches within tissues

Question 10

Clinically risk factors ____ and are therefore _______

Answer 10

Clinically risk factors synergise and are therefore considered together

Question 11

Main Positive Risk Factors of Atheroscelorsis (increase disease risk)

Answer 11

• Hyperlipidaemia: (inc lipids in blood, especially cholesterol)
• Cigarette smoking
• Hypertension
• Diabetes mellitus

**advancing age

Question 12

Additional + risk factors of Atheroscelrosis

Answer 12

Family history (polygenic inheritance)
Male
High sat-fat diet
Stressful & sedentary lifestyle
Obesity & metabolic syndromes
Excess alcohol consumption
Low birth weight
Low Socioeconomic status
Infections

Question 13

What is a risk factor that can be BOTH + and -??

Answer 13

A little alcohol is +
A lot of alcohol is -

Theory is alcohol has some antioxidants

Question 14

Negative Risk factors for Atherosclerosis (decrease risk)

Answer 14

High levels of HDL
Moderate alcohol consumption
Cardiovascular fitness

Question 15

Lipoproteins as powerful risk modifiers for Atherosclerosis

Answer 15

Lipoproteins: lipid core, surrounded by a protein coat (apolipoproteins)
Abnormal blood levels of lipoproteins may alter atherosclerosis risk.

-Cholesterol greatly increases risk
whereas
HDL > decreased risk
LDL > increased risk

Question 16

Whats the pathogenesis of Atherosclerosis

Answer 16

Several theories, but the precise process in uncertain.

Initiation: may involve endothelial cell injury
Progression: is an example of chronic inflammation

1) Endothelial cell injury
2) Leukocyte Migration
3) Smooth Muscle activation and migration
4) Lipoprotein infiltration

Question 17

Endothelial cell injury. Caused by?

Answer 17

Thought to be one of the most important initiators of atherosclerosis

Caused by a combo of injuries or stresses: haemodynamic force of blood(hypertension), chemical insults (smoking, lipids), cytokines

Caused most predominantly at BV junctions

Question 18

Endothelial cell injury may lead to…

Answer 18

• Altered permeability (lipid infiltration)
• Adhesion and activation of leucocytes (due to enhance expression of chemokines and adhesion molecule)
• Activation of thrombosis (turn on blood clot formation)
• In addition endothelial progenitors are recruited

Gradually plaque begins to build up under endothelial cells

Question 19

Leukocyte Migration into the developing plaque

Answer 19

Type of chronic inflammation

1) Circulating monocytes adhere to endothelial cells and enter the atherosclerotic lesion
2) They then differentiate into macrophages
3) Once in the plaque, they ingest large amounts of oxidised lipoproteins which give them a foamy appearance > “foam cells”
4) When they die by necrosis (or apoptosism), their contents including lipoproteins, spill into the extracellular space. (potent activation of inflamm)

Question 20

Smooth muscle cell activation and migration

Answer 20

1) macrophages, platelets and endothelial cells produce growth factors that activate vascular smooth muscle cells

2) Once activated, SM cells proliferate and migrate into the tunica intima from the tunica media
* *accelerated by failure of the IEL

Activated SM:
produces cyto/chemo kines that activated leukocytes
take up lipids
produce ECM proteins

Question 21

Lipoprotein infiltration and oxidation

Answer 21

LP’s become oxidised in plaques. When Endothelial cell is damaged LDL can infiltrate, and is a risk of oxidisation by ROS.

Oxidised lipoproteins:
-attract monocytes > macrophages which injest LDL and form foam cells, as they cannot breakdown the LDL
-stimulate several cell types to release cytokines, inflamm mediators and ROS, growth factors
These cause more dysfunction, inflammation and apoptosis in smooth muscle cells, macrophages and endothelial cells. A viscous cycle

***IEL may be a protective barrier

Question 22

Draw an atheroma lesion

Answer 22

….

Question 23

Pre-clinical to clinical phase of atherosclerosis

Answer 23

Silent phase,
Normal artery progression to an advanced plaque UNTIL they suddenly cause symptoms due to rupture, haemorrhage, thrombosis or dissection.

Question 24

Clinical consequences of atherosclerosis

Answer 24

Myocardial infarction
Peripheral vascular disease
Cerebrovascular disease (strokes)