M103 T3 L16 Flashcards
(57 cards)
Which part of the artery wall do plaques develop in?
tunica intima
What are atherogenic plaques caused by?
the migration of cells from the tunica media to the tunica intima
disrupt the artery wall
What three principle compenents are atherogenic plaques made up of?
Cells
Matrix components
Intracellular and extracellular lipid
What types of cells are atherogenic plaques made up of?
smooth muscle cells
macrophages (foam cells)
T cells
What types of matrix components are atherogenic plaques made up of? (PEC)
proteoglycans
elastic fibres
collagen
What types of intra & extracellular lipid components are atherogenic plaques made up of?
cholesterol
cholesterol esters
What is the effect of the production of NO in a healthy endothelium?
generates an anti-adhesive environment
media promoting relaxation and growth inhibition
What is a condition of an anti-adhesive environment in endothelium?
where the recruitment of monocytes and platelets is inhibited
they won’t adhere to the endothelium layer
Which two properties are associated with the normal endothelium?
anti-coagulant properties
anti-adhesion properties
What are the differences between a normal endothelium and one that has some sort of early damage?
no structural differences - even under a microscope would look the same
functional differences - would function in a different way
What are the functional differences in a damaged endothelium?
loses cell-repellant properties
allows inflammatory cells into the vascular wall
increased permeability to lipoproteins
What is the inflammatory cell type that plays a fundamental role in atherogenesis?
monocytes
What are the roles of monocytes in atherogenesis?
they transform into macrophages under influence of cytokines
they generate Reactive Oxygen Species (ROS)
they produce pro-inflammatory cytokines
What substances attract monocytes to developing plaques?
MCP-1/CCL2
What receptors are expressed by monocytes?
scavenger receptors
Which cytokines transform monocytes into macrophages? (Iffny, Tiffnya, GeM, Mia
IFN-γ
TNF-α
GM-CSF
M-CSF
Where are the cytokines that transform monocytes into macrophages secreted from?
endothelium
vascular smooth muscle cells (VSMC)
What is the effect of ROS on LDL?
they can oxidise LDL in intima
Why are smaller lipoproteins considered more atherogenic than other lipoproteins?
they can enter vascular wall more easily than other particles, due to their size
What are considered smaller lipoproteins?
LDL and remnants
What can happen when lipoproteins enter the vascular wall?
they can be oxidised in the intima
What is the difference between oxidised and normal LDL?
ox’ed stimulates expression of VCAM-1 and MCP-1, which direct monocytes to the lesion sites
it is recognised by the B-100 scavenger receptors on macrophages and is phagocytosed
Which receptor is oxidised LDL recognised by?
the B-100 / scavenger receptors on macrophages
not the normal LDL receptors
What is the process by which macrophages turn into foam cells?
scavenger / B-100 receptors on the macrophage surface recognise oxidised LDL
it is phagocytosed and let it inside the macrophage cell
the oxidised LDL is stored as cholesterol esters in the cytosol that accumulate into lipid drops
AAR, there is a downregulation of the receptors controlling cholesterol export
this messes up the feedback regulation via cholesterol concentration
the macrophages constantly phagocytose the oxidised LDL
the lipids accumulate
turns into foam cell
