Atherosclerosis - 1

Question 1

What are the vaso vasorum and where are they found?

Answer 1

Found in the tunica adventitia and provide this layer of the vessel with nutrients

Question 2

What is atherosclerosis and what does it principally cause? Main pathology

Answer 2

Chronic inflammatory disease, major cause of death in europe, japan and USA.
Principal cause of MI, gangreen and stroke
Characterised by build up of plaque in the artery wall –> causes stiffening and can rupture which is fatal

Question 3

When is inflammation good?

Answer 3

For pathogens, parasites, tumours and wound healing

Question 4

When is inflammation bad?

Answer 4

Arthiritis, Myocardial reperfusion, excessive healing, asthma, shock, atherosclerosis, injury, RESTENOSIS

Question 5

Pathogenesis of atherosclerosis - contributing factors and when does it start? How does it normally trigger?

Answer 5

Many contributing factors - diet, smoking, alcohol consumption, other conditions, haemodynamics
Often begins with injury to the vessel wall and is asymptomatic (once there are symptoms, disease is advancing)

Question 6

What is it referred to as when pathogenesis starts before birth?

Answer 6

Maternal hypercholesterolaemia

Question 7

Atherosclerosis structure - what do lesions normally consist of? How does it impact the vessel?

Answer 7

Lipids, a necrotic core, connective tissue, fibrous cap (which consists of ECMs and VSMCs)
Plaque occludes the vessel lumen and restricts blood flow, and can rupture

Question 8

Plaque distribution - where are they found and what are they governed by?

Answer 8

Focally distributed along the artery in peripheral and coronary arteries
Governed by haemodynamics –> arterial bifurcations impact blood flow, changes in turbulance, changes in blood flow

Question 9

Damage to ECs - Main 3 aspects of injury response - what do they involve

Answer 9

1) Alterations to NO synthesis - impacts blood flow and predisposes to atherosclerosis
2) Signals to inflammatory cells, leads to inflammation and accumulation/migration of inflamm cells
3) Chemoattractants released at site of injury and create a gradient for circulating macrophages to adhere and migrate through vessel wall

Question 10

Fatty streaks - what are they and where are they found

Answer 10

EARLIEST LESION OF ATHEROSCLEROSIS

• Cause accumulation of lipid-laden macrophages (foam cells)
• Found at intimal layer of vessel wall
• cause accumulation of T lymphocytes

Question 11

How do LDLs stimulate athero formation?

Answer 11

Accumulate in the artery wall and become oxidised to form OXLDLs

Question 12

How do ECs stimulate atherosclerosis formation?

Answer 12

Produce free radiacals which oxidise LDLs to form OXLDLs

Question 13

How do OXLDLs stimulate atherosclerosis formation?

Answer 13

Become engulfed by macrophages, via scavenger receptors
This causes formation of FOAM CELLS - these release more cytokines (pro-inflamm factors) triggering a cascade reaction!!!

Question 14

1st STAGE OF ATHEROSCLEROSIS PROGRESSION

Answer 14

Intermediate lesions form

These consist of -foam cells -VSMCs -platelets -Tlymphocytes -pools of EC liquids

Question 15

2nd STAGE OF ATHEROSCLEROSIS PROGRESSION - what is reverse cholesterol transport?

Answer 15

Protective mechanism the body has, acts as a pathway for plaque reduction by collecting cholesterol in the artery wall (HDL)

Question 16

2nd STAGE OF ATHEROSCLEROSIS PROGRESSION - how are HDLs involved in reverse cholesterol transport?

Answer 16

HDLs interact with foam cells via APO-1 particles to collect cholesterol.
Once cholesterol collected, mature HDL released cholesterol at the liver

Question 17

3rd STAGE OF ATHEROSCLEROSIS PROGRESSION

Answer 17

Fibrous plaques form (causes stiffening)
Advanced lesions develop
Cytokines are released by cells which causes deposition of connective tissue and SMC proliferation

Question 18

3rd STAGE OF ATHEROSCLEROSIS PROGRESSION - fibrous cap - what does it contain and what does this result in?

Answer 18

Fibrous cap overlies a rich lipid core and contains:
ECM proteins, SMCs, foam cells, macrophages, apoptotic/necrotic debris
WHen the fibrous cap and core combine this creates the ATHEROMATOUS PLAQUE –> can become calcified, impede blood flow, leads to angina and is prone to rupture

Question 19

4th STAGE OF ATHEROSCLEROSIS PROGRESSION

Answer 19

Plaque erosion (cholesterol cyrstallisation wears off the top of cap like sandpaper), ECs eroded by proteases which break bonds between cells and exposed layer forms thrombus

Plaques are constantly growing and receding –> macrophages increase causing a weakening of the cap….until…
Plaque rupture occurs!!!!

Question 20

WHat occurs upon plaque rupture?

Answer 20

Rupture of plaque provides substrate for thrombus formation and vessel occlusion