Arteriosclerosis Flashcards
What is arteriosclerosis? What is the most common cause?
Generic name for thickening of arterial wall. Atherosclerosis- formation of fatty plaques.
What are the 3 stages of plaque development?
Endothelial damage, uptake of modifies LDLs and macrophage infiltration, smooth muscle proliferation and fibrous cap
What are 4 types of proteins synthesised by the endothelium?
Proteins that affect vasomotor tone, proteins involved in thrombosis, inflammatory factors, cellular adhesion molecules
What are 4 ways the endothelium can be damaged?
Stress, toxic damage, high levels of lipids, infection
How does damage affect the properties of the endothelium?
Inappropriate vasoconstriction, reduced antithrombotic properties
What are the two ways oxidised LDLs are formed?
By reactive oxygen species, by glycation (problem for diabetics)
What do oxidised LDLs do?
Stimulate expression of inflammatory molecules like adhesion molecules for monocytes
How do macrophages infiltrate the endothelium?
Adhesion molecules are inflammatory mediators. Monocytes bind and become macrophages when they cross the endothelium
What are foam cells?
Macrophages that have accumulated lipid droplets
How to macrophages accumulate lipids?
LDL receptor mediated endocytosis
How is a normal LDL particle recognised by a macrophage?
Macrophages have a receptor for the membrane glycoprotein apoprotein B100 on the surface of LDLs. Leads to negative feedback to prevent formation of foam cells
What happens to modified LDLs?
Not recognised by macrophages and absorbed by a scavenger receptor
Why does smooth muscle proliferate?
Endothelial cells and macrophages release growth factors like PGDF
What does the proliferation of smooth muscle do?
Causes breakdown of the internal elastic lamina
How does a fragile fibrous cap form?
PGDF is a chemoattractant for medial smooth muscle