Atherosclerosis

Question 1

What defines atherosclerosis?

NB look at page notes for flow diagram

Answer 1

A disease affecting the innermost layer (TI) of large and medium sized arteries.
It appears as thickenings of lipids and fibrous tissue called plaques.

Question 2

TI

Answer 2

Endothelium and basement membrane; myointimal cells; IEL

endothelium do a lot e.g. contain blood, control clotting and blood pressure

Question 3

What are the main positive risk factors?

Answer 3

hyperlipidaemia (especially cholesterol)
cigarette smoking
hypertension
diabetes
age

Question 4

What are the main negative risk factors?

Answer 4

lots of circulating HDL’s (can carry away cholesterol)
cardiovascular fitness
moderate alcohol consumption( excess is bad)

Question 5

Lipoproteins

Answer 5

Appear to be risk modifiers of atherosclerosis
Are a lipid core surrounded by a protein coat (apolipoproteins). More LDL is positve risk, more HDL is a negative risk factor

Question 6

What is the main pathogenesis of this?

Answer 6

Endothelial cell injury and chronic inflammation.

Question 7

How is endothelial cell injury involved? (thought to be important initiator)

Answer 7

A combination of: hypertension (haemodynamic force, often at branch points), chemical insults (lipids and ciggies) and cytokines.

This may lead to: altered permeablility (lipid infiltration), leukocyte adhesion (expression of adhesion molecules causing inflammation) and thrombosis

Question 8

What role does leukocyte migration play?

Answer 8

A type of chronic inflammation:
Monocytes adhere and differentiate in macrophages.
Macrophages ingest lipoproteins - foam cells
They die by necrosis and apoptosis further causing inflammation (emptying of lipids etc)
Mast cells degrade the Good HDL and promote cell migration

Question 9

What is important about smooth muscle cell activation?

Answer 9

The macrophages, endothelial cells and platelets activate SM cells
They proliferate and migrate from TM to TI. May be accelerated by IEL degradation.
Become secretory, and produce cytokines, chemokines and extracellular matrix. (activates leukocytes). Also take up lipds

Question 10

What happens with lipoprotein infiltration and oxidation?

Answer 10

In plaques, lipoproteins are oxidised, causing monocyte attraction, stimulate cells to secrete growth factors and cytokines and can cause dysfunction and apoptosis. All these contribute to the formation of the atherosclerotic plaque.

Question 11

What are the consequences of atherosclerosis?

Answer 11

Plaques can become unstable- a thin fibrous cap, high lipid content, inflammation
These may rupture, haemorrhage, thromobosis or dissection.

Myocardial infarction, stroke and peripheral vascular disease.