Atherosclerosis Flashcards
Where does atherosclerosis come from?
Greek- athero= paste
sclerosis= hardness
Coat thickens so much as to close up and stop blood movement
Why can atherosclerosis result in?
Heart attack, stroke and gangrene
Initially thought of and what is it now known as?
Initially- lipid storage disease
now- chronic inflammatory disease influenced by many factors= inflammatory cells and cytokines
Main problem with atherosclerosis
If the plaque ruptures- thrombosis formation and death
Pathogenesis
Lifestyle choices, medical conditions and haemodynamic of blood flow
begin at birth but develops over lifetime
often remains symptomless for majority of life until advanced
Risk factors
Modifiable- physical inactivity, stress, obesity, diabetes, dyslipidaemia, hypertension, smoking
Non- modifiable- genetics, gender, age, inflammation, family history
Distribution of atherosclerotic plaque
Found within the peripheral and coronary arteries
focal distribution along the artery length
-may be governed by haemodynamics= changes in tuburlance/flow
- alter gene expression
- areas prone to atherosclerosis
Atherosclerosis is composed of what
Complex lesion consisting of: lipids necrotic core connective tissue fibrous cap- made from SMC and ECM
What happens if the plaque occludes
restrict blood flow- angina
or it may rupture- thrombus formation/ death
Response to injury hypothesis of atherosclerosis
First suggested in 1856- Rudolph Virchow and updated by Russell ross in 1993/9
indicated by an injury in the endothelial cells which leads to endothelial dysfunction
What does healthy endothelium produce to protect against atheroma?
NO and other mediators which protect
alter NO biosynthesis- affects BP control, regional blood flow, predisposes to atherosclerosis
send signals to inflammatory cells which accumulate and migrate into the vessel, leading to inflammation
Stimulus adhesion
Chemoattractants
chemicals that attract leukocytes are released from the site of injure and a concentration gradient is produced
damaged EC also express adhesion molecules
the adhesion cascade
Capture rolling slow rolling firm adhesion transmigration - following down vessel wall and migrate through by chemoattractant
LDL passing though and out of the arterial wall- When?
when in excess, accumulate in the arterial wall- deliver cholesterol
What generate free radicals
Macrophages and EC
LDL is oxidised by and what happens?
free radicals (oxLDL)- engulfed by macrophages to form foam cells release more proinflammatory cytokines
Cytokines found in plaques
IL-1,6,8,IFN-g, TGF-b, MCP-1 and PDGF
Progression of atherosclerosis 1- fatty streaks, what happens?
- earliest lesion of atherosclerosis
- appear at very early age
- accumulation of lipid laden macrophages (foam cells) and T lymphocytes within the intimal layer of the vessel wall form fatty streaks
- damage endothelium- allow macrophages in
progression of atherosclerosis 2- intermediate lesions?
layers composed of:
- foam cells
- VSMC
- EC lipids and cholesterol
- T lymophocytes
- adhesion and aggregation of platelets to vessel wall
progression of atherosclerosis 3- protective mechanism
reverse cholesterol transplant
- pathway for plaque reduction involving HDL
- HDL contain apo-A1 interact with foam and collect cholesterol
- mature HL travels to liver and releases cholesterol
- HDL then recirculates back
progression of atherosclerosis 4- fibrous plaque or advanced lesion
- thought to need an added impetus= another risk factor or area of disturbed flow
- cytokine release cells cause SMC proliferation and deposition of connective tissue
- leads to dense fibrous cap
What is fibrous cap composed of?
ecm- collagen (strength) and elastin (flexibility)
Lipid core
Necrotic and apoptotic debris, smc, foam cells, macrophages, t lymphocytes
Cap and core=
Artheromatous plaque