Atherosclerosis pathology Flashcards
Major characteristics of atherosclerosis (what does it affect, location)
-large and medium sized arteries -patchy plaques/thickenings in the INTIMA of arterial wall -
plaques “atheromas”
- what do they contain
- consequences
- patchy thickenings of arterial wall
- lipids, collagen fibers (ECM), inflammatory cells
- consequences: thrombosis, stenosis, weakness of arterial media
- can result in MI, stroke, peripheral vascular disease
What causes atheroscleoris to be patchy?
depends on flow
High laminar shear endothelial cells = orotection from atherosclerosis
- anti-inflamatory, quiescent, alightment in direction of flow
endothelial cells in area with disturbed shear have proinflammatory = high susceptibility to atherosclerosis
low wall shear stress = makes plaque progress
high WSS - makes plaque break off or fissure
Endothelial shear stress
- tangential force/ unit area on endothelial surface of arterial wall by flowing blood
- mechanoreceptors of ECs sense low ESS –> activate NF-kB –> integrins, cadherines, ion channels, proliferation, etc
Describe process of what happens when you move from steady laminar flow to disturbed flow
-what happens to smooth muscle cells, what factors are released, etc.
- steady: smooth muscle cells stay in media and dont move
- disturbed: tissue factor favors formation of thrombi, see SMCs moving from media into the intima, become part of plaque
In order, what are sites most common for atherosclerosis (5)
- abdominal aorta and iliacs
- coronary arteries
- femoral, popiteals, and thoracic aorta
- internal carotids
- vertebrals, basilar, and circle of willis
What are risk markers for atherosclerosis?
- C-reactice protein (CRP)- sign of inflammation
- MPO
- CD40L
- homocysteine, uric acid, iron, fibrinogen
Use of statins in prevention of major CV events
- seem to reduce indicence of CV events in people with elevated CRP, even if person does not have hyperlipidemia
- rosuvastatin
Core region of plaque
foam cells, necrotic tissue, extracellular lipids (including cholesterol crystals)
Where do you see inflammatory cells most in plaque?
Shoulder areas - lateral sides under cap
proinflammatory cyotkine in plaque
IL-17a
What are TYpe VI / complicated lesions?
type IV and V lesions (lipid core and thick layers of fibrous CT) with disruptions of lesion’s surface, hematoma, hemorrhage, or thrombus
What determines thickness of fibrous cap and thus its vulnerability?
-myofibroblasts
if plaque has lipid rich necrotic core and few secreting myofibroblasts, its vulnerable to fissure and rupture
shear and cyclic forces will compress plaque during systole
4 possible causes of atherosclerosis
- bacteiral or viral infections of arterial wall
- endothelial cell dysfunction
- lipoprotein entry into intima
- arterial wall inflammation
Main infections causing artherosclerosis
- chlamydia pneumoniae
- helicobacter pyloria
- bacteria causing periodontitis
- Cytomegalovirus
- herpes zoster
- hepatitis
Plasticity of macrophages
