Atherosclerosis Flashcards
underlying cause of all stages of atherosclerosis
endothelial dysfunction
can affect many vascular beds
atherosclerosis
rupture of atherosclerotic plaque
MI
1st stage in atherosclerotic plaque formation
endothelial dysfunction
decrease in NO
increase in selectins and integrins
monocytes in
EC apoptosis
endothelial dysfunction
MCP-1
attracts monocytes
M-CSF
attracts macrophages
2nd stage of atherosclerotic plaque
formation of fatty streak
platelets show up and aggregate
VSMC migration by PDGF
T cells show up
foam cell formation
formation of fatty streak
VSMC migrate into endothelium by
PDGF and AngII
macrophages unable to break down oxLDL
foam cell formation
3rd stage in atherosclerotic plaque
formation of fibrous cap (advanced complicated lesions)
VSMC grow over (fibrous cap)
necrosis and apoptosis from MMPs, ROS, oxLDL mediated cell damage
formation of advanced complicated lesions
degrade matrix
MMPs (matrix metalloproteins)
4th stage of atherosclerotic plaque
unstable plaque forms
cap unstable–> rupture
unstable plaque
what makes unstable plaque
VSMC’s die on surface and wall thins
thin cap
MMP activity
VSMC death
lipid rich plaque
vulnerable plaque (unstable)
thick cap
VSMC content high
low MMP activity
lipid poor plaque
stable plaque
stable plaque consequences
angina and intermittent claudication (transient)
unstable plaque consequences
MI
ischemic stroke
CV death
endothelial dysfunction
dyslipidemia
inflammation
oxidative stress
PDGF, Ang II, AGEs
VSMC dysfunction
ECM remodeling
factors that promote atherosclerosis
convert LDL to oxLDL
ROS and AngII
what causes VSMC’s to switch from contractile to migratory and synthetic
AngII, AGE, PDGF
inhibiting dyslipidemia does what to vascular wall
HDL prevents LDL to oxLDL, prevents expression of adhesion molecules, prevents foam cell formation
reducing inflammation does what to vascular wall
no monocytes present (ultimately no foam cell formation)
decreasing oxidative stress does what to vascular wall
NO stays nice and high; no ROS
no ROS oxidative stress leads to what
no monocyte adhesion or migration into cell; no endothelial dysfunction
decrease in endothelial dysfunction does what to vascular wall
NO normal (no EC death)
no monocytes, no platelet aggregation, no LDL oxidation
place where people normally form atherosclerotic plaques due to change in laminar flow from bifurcation
carotid arteries
decrease in PDGF, AGEs, and AngII does what to vascular wall
STOPS CAP FORMATION
VSMC stays contractile
this is involved in all the steps of atherosclerosis, so if you block this, you won’t get plaque formation
AngII
drug used to lower AngII
Ramapril (ACEI)
increase in VSMC and decrease in ECM remodeling effect on vascular wall
no cap formation
no rupture b/c no MMP activity
drug that blocks AT1R
Telmisartan
AT1R
AngII receptor (ARB)
successful drugs to decrease CV disease
Ramapril and Telmisartan
decrease LDL and CRP=
decrease risk for CV disease
