Atherosclerosis 1 Flashcards
What is the structure of an arterial wall?
Tunica intima- endothelial layer, healthy= 1 cell thick
media- several cells thick, VSMCs
adventitia- connective tissue and small capillaries- vasothorum- gives blood to the outer edge of the artery
*internal and external elastic lamina
Examples of inflammatory disease
Asthma Ischaemic heart disease arthritis atherosclerosis restenosis- can happen when you treat atherosclerosis
What is atherosclerosis?
Build up of plaque in the arterial wall that stiffens it
principal cause of heart attack, stroke and gangrene of the extremities
now known to be an inflammatory disease influenced by many factors
main issue is when the plaque ruptures- thrombus and ultimately death
What influences atherosclerosis?
lifestyle choices
medical conditions
hemodynamics- blood flow- turbulent blood flow
When do symptoms appear in atherosclerosis?
often remain symptomless for the majority of life (unless you’re homozygous for a condition)
start of symptoms signals advanced disease
always begins with an initial insult to the arterial wall
What are the modifiable risk factors for atherosclerosis?
diabetes dyslipidemia hypertension obesity smoking/alcohol stress physical inactivity
What are the nonmodifiable risk factors for atherosclerosis?
Genetics gender- male age inflammation family history of CVD
How are atherosclerotic plaques distributed?
ALl over- but mainly sticks to areas of bifurcation
found within peripheral and coronary arteries
focal distribution along the artery length
changes in the flow/distrubance= makes areas more prone to atherosclerosis
What does an atherosclerotic lesion consist of?
Lipid
necrotic core
connective tissue
fibrous cap- SMCs and extracellular matrix
What is the response to injury hypothesis?
Injury to the endothelial cells triggers endothelial dysfunction- drives the initiation of atherosclerosis
Differences between a healthy and atherosclerotic endothelium?
Healthy= has a protective mechanism, separates the blood from everything underneath
produces factors such as NO- which protects against atheroma
Atherosclerotic= alter the biosynthesis of NO- affects BP control, regional blood flow and predisposes to atherosclerosis
start producing inflammatory cytokines- build up in the area and form a concentration gradient- call in WBCs and start an inflammatory response
Examples of cytokines found in plaques
IL-1
IL-6
IL-8
IFN- gamma
What is the adhesion stimulus of atherosclerosis?
A chemoattractive gradient of cytokines attracts macrophages to stick to the endothelium
they stick via selectins and integrins- and start to roll down the vessel wall
roll quickly then slowly
they migrate through the endothelial cells into the vessel wall
How are LDLs a stimulus for atherosclerosis?
LDLs can pass into and out of the vessel wall- depositing cholesterol
in atherosclerosis, they accumulate inappropriately in the wall
endothelial cells and macrophages generate free radicals
LDLs are oxidized by free radicals into oxLDL
oxLDL is engulfed by macrophages- forming foam cells
foam cells go onto release more pro-inflammatory cytokines- calls in more macrophages- cascade reaction
What occurs in the first stage of atherosclerosis?
- Fatty streaks
accumulation of foam cells and T-lymphocytes within the intimal layer- below the endothelium
What occurs in the second stage of atherosclerosis?
- Intermediate lesions
layer of foam cells gets bigger
VSMCs get involved
foam cells apoptose- release cholesterol
fatty streak composed of: foam cells, VSMCs, isolated pools of extracellular lipid/cholesterol, t-lymphocytes
adhesion and aggregation of platelets to the vessel wall
*most people stay at this stage
What is the protective mechanism?
HDLs interact with foam cells- remove cholesterol- balance of lipid going in and out of the artery wall
HDL contains apo-A1 particles that interact with foam cells- collect cholesterol
mature HDL then travels to the liver to release the cholesterol (for excretion)
HDL then recirculates back to the heart
What is the third stage of atherosclerosis?
VSMCs start to move into the intima- develop the fibrous cap= VSMCs and collagen
necrotic core: foam cells, cholesterol crystals, t-lymphocytes
plaque starts to impede blood flow
as plaque bets bigger- symptoms- angina etc
first just in exercise, but then at rest
What is the last stage of atherosclerosis?
Plaque constantly grows and recedes
fibrous cap needs to be reabsorbed and deposited in order to be maintained- as cells die and grow
large number of VSMCs and extracellular proteins stabilize the plaque
large no. of macrophages predisposes the plaque to rupture= increased amounts of matrix metalloproteinases and gelatinase- cap becomes weak
rupture of the cap provides substrate for thrombus formation= vessel occlusion
What is plaque disruption?
The torn cap projects into the lumen of the artery- the thrombus is contained within the plaque core
Features of plaque rupture
thin fibrous cap collagen poor cap large lipid core many macrophages fibrin-rich thrombus
Features of eroded plaque
proteoglycan/ glycosaminoglycan rich
little or no lipid core
many SMCs
platelet-rich thrombus - ‘white thrombus’
