Atherosclerosis

Question 1

What is atherosclerosis

Answer 1

Ldlc fatty deposits within inner artery lining causing endothelial dysfunction and vascular inflammation

Question 2

What forms a fatty streak

Answer 2

Foam cell production

Question 3

Why might some older people not get it ever

Answer 3

Dietary differences or genetics

Question 4

What does ageing do to stop endothelial repair by cholesterol damage/damage

Answer 4

Bone marrow progenitors are lost through mutations

Question 5

Which artery mainly does it occur in but others too

Answer 5

Coronary

Question 6

Plaque build up can cause what

Answer 6

Ischemia and then pain due to lack of o2

Question 7

What happens if plaque ruptured

Answer 7

Thrombosis, causes acute artery occlusion causing tissue death and or organ failure

Question 8

What is the inner layer of the artery closest to endothelial layer

Answer 8

Intima
Then media
Then adventitia

Question 9

What cells which make up the media migrate to intima to sustain the plaque

Answer 9

SMCS

Question 10

What can happen in acute obstruction or chronic eg rupture in cerebral arteries

Answer 10

Stroke

Chronic can cause vascular dementia

Question 11

What can happen in acute coronary obstruction

Answer 11

Myocardial infarction/heart attack

Question 12

In chronic renal artery obstruction what can happen

Answer 12

Renal failure or hypertension

Question 13

Give some risk factors

Answer 13

Age
Gender
Hcy
Infection
Hypertension
Smoking
Hypercholesterolemia (major)

Question 14

How is smoking a risk factor

Answer 14

Raises ldlc and also causes predamage by ROS

Question 15

What does angiotensin II (vasoconstrictor) do to cause risk

Answer 15

Increases lipoprotein permeability, and accelerate ldl oxidation

Question 16

Why would infection be a risk factor

Answer 16

Already a pro inflammatory environment

Question 17

What hypothesis is the start of atherosclerosis

Answer 17

Response to injury by endothelial cells

Eg from hypertension/turbulent flow, hyper cholesterol, hcy, ros circulation

Question 18

What do endothelial cells start to express in the response to injury

Answer 18

Vcam1 and icam1 for leukocyte recruitment and adhesion

Aswell as chemoattractant gradients

Question 19

What is a major chemokine released from endothelial cells which binds ccr2 on monocytes

Answer 19

Mcp-1

Question 20

When is vcam1 expressed more for lymphocyte recruitment

Answer 20

Hyperlipidemia

Or inflam cytokines like il1 and tnfa (feedback cycle)

Question 21

What types of receptors are upregulated on macrophages which bind oxldl

Answer 21

Scavenger receptors

Question 22

When cytoplasmic lipids are endocytosed foam cells form. How do they form the necrotic lipid core of plaques

Answer 22

They die via apoptosis

Question 23

How are T cells activated and what do they release

Answer 23

Oxldl presentation

Release cytokines like TNFa and il1

Question 24

How do they promote mmp release by macrophages

Answer 24

Cd40 binding to cd154

Question 25

What promotes production of gf pdgf and fgf for smc migration and proliferation

Answer 25

The TNFa and il1

Question 26

How does smc form fibrous cap

Answer 26

Release ecm eg collagen

Question 27

How can microvessels which may be site of thrombosis form in plaques

Answer 27

Vegf local production

Question 28

What promotes mmp release allowing for fibrous cap fracturing

Answer 28

The pro inflam cytokines

Question 29

Explain how thrombosis occurs

Answer 29

When it ruptured, blood can come into contact with tissue fsctor in the lipid core which is pro coagulation The coagulation cascade produces thrombin which activates platelets = produce a thrombus blood clot

Question 30

How does it layer cause thickening of plaque/chronic occlusion further

Answer 30

Thrombin stimulates platelets to release pdgf and tgfb which allows smc prolif and collagen production = chronic ischemia

Question 31

Mutations in what can increase hyperlipidemia/cholesterol in the blood

Answer 31

LDL receptor or apoe Apoe binds ldl receptor on liver and allows ldlc endocytosis reducing levels in blood

Question 32

How can self reactive T cells to apoB contribute to atherogenesis

Answer 32

They can start to self react to apoB which is part of the ldlc complex This stimulates more inflammation in ldlc response

Question 33

Give 3 ways ldlc can be reduced for therapy

Answer 33

Ezetimibe Statins Pcsk9 inhibitors

Question 34

What does ezetimibe do

Answer 34

Stop absorption of micelles in intestines

Question 35

What do statins do

Answer 35

Prevent conversion of acetyl coa to cholesterol

Question 36

What does pcsk9 do

Answer 36

Stimulates ldl receptor degradation in endsoome. Stops ldlc absorption into liver

Question 37

What sort of pcsk9 mutations been found

Answer 37

Gof Lof (protection)

Question 38

What type of therapy used to block it and needs to be re injected every 4 weeks

Answer 38

Mab

Question 39

Why would presence of cells like macrophages cause more ldl oxidation

Answer 39

Ros release