Atherosclerosis - Quiz 3 Flashcards
atherosclerosis accumulation of
within
- progressive accumulation of smooth muscle cells
- lipids
- connective tissue
- within intima
progressive accumulation of smooth muscle cells, lipids, and connective tissue within intima results in
- intimal thickening with atheroma formation
another name for atheroma
- fibrofatty plaque
what can cause ischemia
- narrowing of vessel lumen
atherosclerosis affect on tunica intima
- weakening of tunica intima
what accounts for >50% annual mortality in the US
- major complication of atherosclerosis
what is the leading cause of death in the US
- ischemic heart disease
layers of normal vascular anatomy impacted by atherosclerosis
- intima
- media
constituents of normal vascular anatomy impacted by atherosclerosis
- endothelial cells
- smooth muscle cells
- extracellular matrix
extracellular matrix composed of
- elastin
- collagen
- glycosoaminoglycans
atherosclerosis affects which artery types
- large (elastic)
- medium (muscular)
examples of large elastic arteries
- aorta
- pulmonary
examples of medium muscular arteries
- coronary
- renal
atherosclerosis is centered in
- vascular wall
atherosclerosis is triggered by
- altered lipid metabolism
atherosclerosis is mediated by
- endothelial dysfunction
contribution factors to the pathogenesis of atherosclerosis
- chronic endothelial injury
- accumulation of lipoproteins
- oxidation of accumulated lipoproteins
- recruitment of inflammatory cells
- generation and release of growth factors
- proliferation and migration of cells
chronic endothelial injury due to
- endothelial dysfunction
which lipoproteins are accumulated
- LDL
which inflammatory cells are recruited?
- monocytes/macrophages
- lymphocytes
recruitment of inflammatory cells leads to
- foam cell formation
- fatty streaks
which cells undergo proliferation and migration
- smooth muscle cells
- fibroblasts
result of proliferation and migration of smooth muscle cels and fibroblasts
- fibrous plaque and complex atheroma formation
chronic endothelial injury due to these conditions
- hyperlipidemia
- hypertension
- smoking
- homocysteine
- hemodynamic factors
- toxins
- viruses
- immune reactions
endothelial cell function
- decreased permeability
- anticoagulant/antithrombotic
- vasodilators
- growth inhibitors
D VAG
endothelial cell dysfunction
- increased permeability
- procoagulant/prothrombotic
- vasoconstrictors
- inflammation
- growth promoters
VIPIG
endothelial dysfunction causes increased permeability for
- leukocytes/monocyte adhesion and emigration
- platelet adhesion
- lipid deposition
LDL modifications
- lipid oxidation
- ApoB fragmentation
- glycation
- immune complexes
these ENHANCE LDL accumulation in macrophages and peripheral tissues
importance of LDL modifications
- increase affinity for scavenger receptors on macrophages
- make LDL stay in periphery instead of go back to the liver
effects of LDL modifications
- increased adhesion molecule expression
- expression of chemokine, Ck receptors
- amplification of platelet activation
release of factors from activated platelets, macrophages, or vascular cells leads to
- smooth muscle emigration from media to intima
- macrophage activation
intimal/medial thickening: response to vascular injury
- proliferative factors
- neointima formation
neointima formation involves in a change in
- smooth muscle cell phenotype
- fibroblast proliferation and collagen production
changes in smooth muscle cell phenotype
- lose contractility
- gain proliferative and migratory capacity
- gain the ability to synthesize extracellular matrix
once macrophages have been activated
- macrophages and smooth muscle cells engulf lipid
- inflammation
HOW TF DO SMOOTH MUSCLE CELLS ENGULF THINGS.
cytokine balance in atherogenesis
- tip toward pro inflammatory cytokines
after macrophages and smooth muscle cells engulf lipid and inflammation occurs
- smooth muscle proliferation
- collagen and other ECM deposition
- extracellular lipid
- form the fibrofatty atheroma
classic atheroma
- raised focal intimal plaque with necrotic lipid core covered by fibrous cap
constituents of classic atheroma
- cells
- connective tissue extracellular matrix
- lipid
cells - constituents of classic atheroma
- smooth muscle cells
- macrophages
- leukocytes
connective tissue extracellular matrix - constituents of classic atheroma
- collagen
- elastic fibers
- proteoglycans
lipid - constituents of classic atheroma
- cholesterol and cholesterol esters
- intracellular and extracellular
center of larger plaques may contain
- yellow grumous debris
- atheroma
fibrous cap composed of
- smooth muscle cells
- macrophages
- foam cells
- lymphocytes
- collagen
- elastin
- proteoglycans
- neovascularization
necrotic center composed of
- cell debris
- cholesterol crystals
- foam cells
- calcium
progression of atherosclerosis
- normal artery
- fatty streak
- fibrofatty plaque
- advanced vulnerable plaque
clinical phase progression of atherosclerosis
- aneurysm and rupture
- occlusion by thrombus
- critical stenosis
aneurysm and rupture can happen by
- mural thrombosis
- embolization
- wall weakening
occlusion by thrombus can happen by
- plaque rupture/erosion/hemorrhage
- mural thrombosis
- embolization
critical stenosis can happen by
- progressive plaque growth
what kind of lesion is the fatty streak
- early lesion
fatty streak possible precursor of
- arthroma
is the fatty streak raised?
- not significantly
fatty streak disturbance of blood flow
- no disturbance of blood flow
fatty streak composed of
- lipid-filled foam cells
- with t lymphocytes
- and extracellular lipid within intima
aortic fatty streaks seen in most western country children by what age?
- 10
what stage lesion is the fibrofatty plaque
- intermediate
fibrofatty plaque raised
- focal raised lesions causing disturbance of blood flow
fibrofatty plaque composed of
- fibrous cap
- lipid core
what stage of lesion is the complicated lesion
- advanced
calcification of complicated lesions
- patchy or massive calcification
results of complicated lesion
- focal rupture or ulceration of luminal surface
- intra-plaque hemorrhage
- superimposed thrombosis
- weakening of tunica intima
focal rupture or ulceration of luminal surface can cause
- exposure of thrombogenic constituents
- atheroembolization
intra-plaque hemorrhage may induce
- plaque rupture
what may cause weakening of tunica media
- thinning of tunica media
- loss of elastic tissue with aneurysmal dilation
process of fatty streak development
- endothelial dysfunction
- lipoprotein entry and modification
- leukocyte recruitment
- foam cell formation
endothelial dysfunction
- secondary to shear stress
- increased LDL concentration
lipoprotein entry and modification
- intimal accumulation of LDL proteins
- oxidation and glycation of lipoproteins
leukocyte recruitment
- endothelial cells and smooth muscle cells induce expression of adhesion molecules and release chemoattractants
- increase monocytes
- increase T cell recruitment
foam cell formation
- monocytes engulf oxidized LDL and become foam cells
plaque progression process
- intima continues to thicken
- evolution of the fatty streak and calcification
- fibrous capsule
- luminal narrowing
intima continues to thicken due to
- smooth muscle cell proliferation
- increased leukocyte recruitment
fibrous capsule due to
- smooth muscle cell apoptosis
- lipid rich core surrounded by fibrous capsule
luminal narrowing
- plaque growth into lumen causes flow limitation
result of luminal narrowing
- claudication
- angina
claudication will occur if flow limitation is in
- peripheral vessels
angina will occur if flow limitation is in
- coronary circulation
which fibrous capsules are more stable
- thicker
- cause more narrowing through
which types of lesions are reversible
- those leading to fatty streak development
complications of atherosclerosis
- ischemia (due to luminal stenosis)
- acute infarcts (due to acute thombosis, atheroembolization or thromboembolism)
- artery remodeling (leads to aneurysm formation and/or rupture)
complications of atherosclerosis - ischemia due to
- luminal stenosis
complications of atherosclerosis - acute infarcts due to
- acute thrombosis secondary to plaque rupture or intra-plaque hemorrhage
- embolization of plaque fragments or thrombus
major complications of atherosclerosis
- MI
- sudden cardiac death
- chronic ischemic heart disease
- aortic aneurysms
- cerebral infarction
- ischemic encephalopathy
- PVD
- mesenteric occlusion
arterial distribution of atherosclerosis from highest to lowest incidence
- abdominal aorta
- coronary arteries
- popliteal arteries
- descending thoracic aorta
- internal carotids
- circle of willis
modifiable risk factors for atherosclerosis
- smoking
- hypertension
- dyslipidemia
- diabetes
- sedendary lifestyle
non-modifiable risk factors for atherosclerosis
- age
- sex
- family history/genetics
what hormone is protective against atherosclerosis
- estrogen
Characteristics of Unstable Plaque/Plaque Rupture
- Thin fibrous cap
- Intense Inflammation
- High Oxidative Burden
- Abundant Macrophages
- Large Lipid Core
- Increased MMPs/TF
Characteristics of a Stable Plaque (not likely to rupture)
- Thick Fibrous Cap
- Mild Inflammation
- Mild Oxidative Burden
- Low Macrophage Content
- Small Lipid core
Progression of (Coronary) Atherosclerosis
From Pre-Clinical Phase to Clinical Phase
Pre-Clinical Phase:
-Normal artery > Fatty Streak > Fibrofatty Plaque > Advanced Plaque
Clinical Phase:
- Aneurysm and Rupture
- Occlusion by Thrombus
- Critical Stenosis
Vulnerable plaques are prone to
erosion or rupture, and therefore thrombus formation
The presence of a Fibrous Cap and Lipid Core occurs in
Fibrofatty Plaque (after fatty streak)
What do you see in a Fatty Streak
Lipid-filled foam cells with T lymphocytes and extracellular lipid within intima
Endothelial Cell Properties/Functions (7)
- Maintenance of Permeability Barrier
- Modulate Coagulation (Anticoag/Antithrombotic/Fibrinolytic v. Prothrombotic)
- ECM Production (collagen, proteoglycans)
- Modulate Blood Flow and Vascular Reactivity
- Regulate Inflammation/Immunity
- Regulate Cell Growth
- Oxidation of LDL
