Atherosclerosis Flashcards
Atherosclerosis is a chronic ______ response in the walls of arteries associated with collection of ______ that accumulate _____ (primarily cholesterol, from LDL) and _____ ______ deposits from fibroblasts.
A chronic inflammatory response in the walls of arteries associated with collection of macrophages that accumulate lipids (primarily cholesterol, from LDL) and collagen matrix deposits from fibroblasts.
steps in development of atherosclerosis
- Endothelial cell injury
- Macrophage and lymphocyte migration
- Lipid accumulation, smooth muscle-fibroblast proliferation
- Plaque structure evolution
Injury of vascular endothelium results in ______ cell activation and produces a pro-_______, pro-_____ state
Injury of vascular endothelium results in endothelial cell activation and produces a pro-thrombotic, pro-atherogenic state
endothelial cell injuries
- HTN (mechanical stress)
- Flow disturbance (slow, turbulent flow)
- Smoking, pollution (?)
- Hyperglycemia
- High LDL concentration (oxidized LDL, small dense LDL)
- Immune injury
_______ cells express selective _______ molecules that bind ______ and inflammatory mediators
Endothelial cells express selective adhesion molecules that bind monocytes and inflammatory mediators
what 2 things migrate between endothelial cells and localize in the intima (space between EC and basement membrane)
macrophages and lymphocytes
what engulf LDL, especially oxidized LDL
macrophages
What is LDL oxidized by?
- oxygen free radicals (inflammation)
- slow and turbulent blood flow
What is LDL enhanced by?
-small size of LDL –> “small dense LDL”
What become activated and promote chronic inflammation?
T lymphocytes
What do activated macrophages do to LDL
phagocytose LDL
What does phagocytosis of LDL cause?
release of O2 radicals
What does the release of O2 radicals do to LDL?
oxidize addition LDL, further increasing LDL uptake
What does the activation of macrophages and LDL uptake result in?
- lipid inclusions in macrophages
- secrete growth factors
What are lipid rich macrophages?
foam cells
_______ macrophages release ______, forming ____ _____ of atherosclerotic lesion.
Dying macrophages release lipids, forming lipid core of atherosclerotic lesion.
What do growth factors promote?
promote migration and proliferation of smooth muscle and fibroblasts into lesions
Dense collagen-rich matrix from smooth muscle and fibroblasts
superficial fibrous cap
actively expanding edge of the lesion
“shoulder” of cap
What makes up the central core? (3)
- Lipid-containing foam cells
- Fatty debris (lipid core, cholesterol crystals)
- Necrotic cellular debris
Unstable plaques contain:
- Large lipid core or intraplaque hemorrhage
- Thin or easily ruptured cap
- Marked inflammatory component
Stable plaques contain:
- Mainly fibrous with thick continuous fibrous cap
- Small or no lipid core
- Little sign of inflammation
large lipid core or intraplaque hemorrhage
unstable plaque
small or no lipid core
stable plaque
thin or easily ruptured cap
unstable plaque
mainly fibrous with thick continuous fibrous cap
stable plaque
marked inflammatory component
unstable plaque
little sign of inflammation
stable plaque
What type of plaque is more likely to rupture, resulting in thrombosis ± embolus formation? i.e. MI
unstable plaque
What type of plaque is more likely to result in gradual stenosis and tissue ischemia? i.e. angina, claudication
stable plaque
What does increase in plaque size cause? (3)
- arterial dilation
- arterial wall thickening and plaque enlargement
- stenosis
Regarding plaque size increase, what does arterial dilation result in?
minimal internal diameter change (positive remodeling, an early response)
Regarding plaque size increase, what does arterial wall thickening and plaque enlargement result in?
internal diameter reduction (negative remodeling)
Regarding plaque size increase, what does stenosis result in?
reduction in internal diameter for any reason, including plaque accumulation
gradual thickening of the arterial wall at an area of injury (enhanced healing response)
restenosis
What can insertion of vascular stent or angioplasty cause?
vascular injury, often causing restenosis
What can inhibit restenosis to maintain lumen size longer?
drug-eluding stents
What results in endothelial cell activation and plaque formation?
disruptions in laminar (straight, undisturbed) blood flow
examples of where plaques form when and where flow is disrupted
- Vessel bifurcations (internal/external carotid)
- Vessel branches (circle of Willis, intercostal arteries)
- Areas of blood stasis (Carotid bulb)
Plaques expand in _____, _____, and ____ i.e. remodel
Plaques expand in length, width, and depth i.e. remodel
