Atherosclerosis 1

Question 1

What is the structure of an arterial wall?

Answer 1

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

Question 2

Examples of inflammatory disease

Answer 2

Asthma
Ischaemic heart disease 
arthritis 
atherosclerosis
restenosis- can happen when you treat atherosclerosis

Question 3

What is atherosclerosis?

Answer 3

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

Question 4

What influences atherosclerosis?

Answer 4

lifestyle choices
medical conditions
hemodynamics- blood flow- turbulent blood flow

Question 5

When do symptoms appear in atherosclerosis?

Answer 5

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

Question 6

What are the modifiable risk factors for atherosclerosis?

Answer 6

diabetes
dyslipidemia 
hypertension 
obesity 
smoking/alcohol 
stress
physical inactivity

Question 7

What are the nonmodifiable risk factors for atherosclerosis?

Answer 7

Genetics
gender- male 
age
inflammation 
family history of CVD

Question 8

How are atherosclerotic plaques distributed?

Answer 8

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

Question 9

What does an atherosclerotic lesion consist of?

Answer 9

Lipid
necrotic core
connective tissue
fibrous cap- SMCs and extracellular matrix

Question 10

What is the response to injury hypothesis?

Answer 10

Injury to the endothelial cells triggers endothelial dysfunction- drives the initiation of atherosclerosis

Question 11

Differences between a healthy and atherosclerotic endothelium?

Answer 11

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

Question 12

Examples of cytokines found in plaques

Answer 12

IL-1
IL-6
IL-8
IFN- gamma

Question 13

What is the adhesion stimulus of atherosclerosis?

Answer 13

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

Question 14

How are LDLs a stimulus for atherosclerosis?

Answer 14

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

Question 15

What occurs in the first stage of atherosclerosis?

Answer 15

1. Fatty streaks

accumulation of foam cells and T-lymphocytes within the intimal layer- below the endothelium

Question 16

What occurs in the second stage of atherosclerosis?

Answer 16

2. 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

Question 17

What is the protective mechanism?

Answer 17

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

Question 18

What is the third stage of atherosclerosis?

Answer 18

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

Question 19

What is the last stage of atherosclerosis?

Answer 19

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

Question 20

What is plaque disruption?

Answer 20

The torn cap projects into the lumen of the artery- the thrombus is contained within the plaque core

Question 21

Features of plaque rupture

Answer 21

thin fibrous cap
collagen poor cap
large lipid core
many macrophages 
fibrin-rich thrombus

Question 22

Features of eroded plaque

Answer 22

proteoglycan/ glycosaminoglycan rich
little or no lipid core
many SMCs
platelet-rich thrombus - ‘white thrombus’