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chronic disease > Atherosclerosis > Flashcards

Atherosclerosis Flashcards

1
Q

What is atherosclerosis

A

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

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2
Q

What forms a fatty streak

A

Foam cell production

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3
Q

Why might some older people not get it ever

A

Dietary differences or genetics

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4
Q

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

A

Bone marrow progenitors are lost through mutations

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5
Q

Which artery mainly does it occur in but others too

A

Coronary

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6
Q

Plaque build up can cause what

A

Ischemia and then pain due to lack of o2

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7
Q

What happens if plaque ruptured

A

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

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8
Q

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

A

Intima
Then media
Then adventitia

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9
Q

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

A

SMCS

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10
Q

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

A

Stroke

Chronic can cause vascular dementia

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11
Q

What can happen in acute coronary obstruction

A

Myocardial infarction/heart attack

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12
Q

In chronic renal artery obstruction what can happen

A

Renal failure or hypertension

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13
Q

Give some risk factors

A

Age
Gender
Hcy
Infection
Hypertension
Smoking
Hypercholesterolemia (major)

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14
Q

How is smoking a risk factor

A

Raises ldlc and also causes predamage by ROS

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15
Q

What does angiotensin II (vasoconstrictor) do to cause risk

A

Increases lipoprotein permeability, and accelerate ldl oxidation

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16
Q

Why would infection be a risk factor

A

Already a pro inflammatory environment

17
Q

What hypothesis is the start of atherosclerosis

A

Response to injury by endothelial cells

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

18
Q

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

A

Vcam1 and icam1 for leukocyte recruitment and adhesion

Aswell as chemoattractant gradients

19
Q

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

A

Mcp-1

20
Q

When is vcam1 expressed more for lymphocyte recruitment

A

Hyperlipidemia

Or inflam cytokines like il1 and tnfa (feedback cycle)

21
Q

What types of receptors are upregulated on macrophages which bind oxldl

A

Scavenger receptors

22
Q

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

A

They die via apoptosis

23
Q

How are T cells activated and what do they release

A

Oxldl presentation

Release cytokines like TNFa and il1

24
Q

How do they promote mmp release by macrophages

A

Cd40 binding to cd154

25
Q

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

A

The TNFa and il1

26
Q

How does smc form fibrous cap

A

Release ecm eg collagen

27
Q

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

A

Vegf local production

28
Q

What promotes mmp release allowing for fibrous cap fracturing

A

The pro inflam cytokines

29
Q

Explain how thrombosis occurs

A

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

30
Q

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

A

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

31
Q

Mutations in what can increase hyperlipidemia/cholesterol in the blood

A

LDL receptor or apoe

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

32
Q

How can self reactive T cells to apoB contribute to atherogenesis

A

They can start to self react to apoB which is part of the ldlc complex

This stimulates more inflammation in ldlc response

33
Q

Give 3 ways ldlc can be reduced for therapy

A

Ezetimibe
Statins
Pcsk9 inhibitors

34
Q

What does ezetimibe do

A

Stop absorption of micelles in intestines

35
Q

What do statins do

A

Prevent conversion of acetyl coa to cholesterol

36
Q

What does pcsk9 do

A

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

37
Q

What sort of pcsk9 mutations been found

A

Gof

Lof (protection)

38
Q

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

A

Mab

39
Q

Why would presence of cells like macrophages cause more ldl oxidation

A

Ros release

chronic disease (16 decks)

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