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Y2 BRS (Haroop) > Atherosclerosis and heart disease > Flashcards

Atherosclerosis and heart disease Flashcards

1
Q

What are the modifiable risk factors of heart disease?

A
  • Smoking
  • Lipids intake
  • Blood pressure
  • Diabetes
  • Obesity
  • Sedentary lifestyle.
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2
Q

What are the non-modifiable risk factors of heart disease?

A

Age, sex and genetic background

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3
Q

What three factors when combined increase heart disease risk exponentially?

A

1) Smoking
2) Hypertension
3) High cholesterol

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4
Q

What happens to low density lipoproteins once deposited in the subintimal space?

A

Binds to matrix proteoglycans and becomes oxidised by reactive oxygen species released by macrophages

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5
Q

What is the step of atherosclerosis?

A

Coronary artery at lesion-prone location (adaptive thickening of smooth muscle)

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6
Q

What is a type II lesion?

A

Macrophage transmigration into the subendothelial space, phagocytosis oxidised lipoproteins forming foam cells.

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7
Q

What is a type III lesion?

A

Preatheroma: Small pools of extracellular lipid

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8
Q

What is a type IV lesion?

A

Atheroma - core of extracellular lipid forms

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9
Q

What is a type V lesion?

A

Fibroatheroma, progressive fibrosis; thickening the fibrous cap; separating the lipid core from the lumen

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10
Q

What is a complicated lesion?

A

Fissure and haematoma and thrombus formation

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11
Q

How do complications arise due to plaque formation?

A

Due to extensive growth of the lipid cores, narrowing the lumen (stenosis or plaque ruptures)

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12
Q

When is the window of opportunity for primary prevention?

A

Intermediate and advanced lesions

Life-style changes
Risk factor management

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13
Q

What is the intervention of arterial stenosis?

A

Balloon angioplasty PCI

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14
Q

What is the function of vascular endothelial cells?

A

Barrier function (to lipoproteins)

Leukocyte recruitment

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15
Q

What is the function of monocytes/macrophages?

A

Foam cell formation

Cytokine and growth factor release

Major source of free radicals

Metalloproteinases

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16
Q

What is the function of vascular smooth muscle cells?

A

Migration and proliferation within the tunica media

Collagen synthesis

Remodelling and fibrous cap formation

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17
Q

What is the function of platelets?

A

Thrombus generation - presents in acute MI, and unstable angina

Cytokine and growth factor release

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18
Q

What is the function of T-lymphocyte?

A

Macrophage activation

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19
Q

Which type of treatment during clinical trials had fewer major adverse cardiovascular events (MACE)?

A

Anti-Il-1 treatment

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20
Q

Which CD macrophage lysosome protein is brown-dyed when associated wot an antibody?

A

CD68

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21
Q

How are macrophage subtypes regulated?

A

Combination of transcription factors binding to regulatory sequences of DNA

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22
Q

What is the main function of inflammatory macrophages?

A

Phagocytose pathogens

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23
Q

What are the three classes of resident macrophages?

A

Alveolar resident macrophages

Osteoclasts

Spleen (reticuloendothelial)

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24
Q

Where are LDLs synthesised?

A

Within the liver

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25
Q

What do LDLs transport?

A

Cholesterol

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26
Q

Where is cholesterol abnormally deposited?

A

Arterial intima

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27
Q

What are the docking molecules that assist with lipid binding?

A

Apoproteins

28
Q

What are contained within LDL micelles?

A

Cholesterol esters

29
Q

Which class of lipoproteins transport cholesterol from the peripheral tissues (arteries) to the liver?

A

High-density lipoproteins (HDLs)

-reverse cholesterol transport

30
Q

What type of transporter are HDLs involved in?

A

Reverse cholesterol transport

31
Q

How are LDLs oxidised?

A

Free radicals are released by activated macrophages

32
Q

What is the fate of cholesterol within the sub-endothelial space?

A

Binds to proteoglycans and ultimately oxidised

33
Q

What extracellular matrix protein binds to cholesterol in the sub-endothelial space?

A

Proteoglycan

34
Q

How does proteoglycan-cholesterol binding influence oxidation?

A

Increases the susceptibility to modification

35
Q

What is familial hyperlipidaemia?

A

An autosomal disorder that impairs lipoprotein metabolism by down-regulating LDL receptor expression

36
Q

What is the effect of the down-regulation of LDL receptors?

A

Diminishes the clearance of LDLs from the plasma

Massively elevated cholesterol (20mmol/L)

Excessive production of VLDLs .

37
Q

Which type of protein is retained within the sub-endothelial space in FH?

A

Apolipoprotein B-100

Retained due to interactions with the extracellular matrix. Therefore, this allows reactive oxygen species to modify the surface phospholipids and unesterified cholesterol.

38
Q

How are circulating LDLs ingested in FH?

A

By unregulated scavenger receptors

39
Q

What are the presentations of FH?

A

Xanthomas and atherosclerosis

40
Q

What is a xanthoma?

A

Yellow plaques that occur predominantly besides the inner canthus of the eyelide

41
Q

How is cholesterol regulated?

A

Negatively regulated by cellular cholesterol (LDL-receptors are sensitive to extracellular serum cholesterol), and are present on the cell surface membrane of hepatocytes

42
Q

Which receptors are sensitive to extracellular serum cholesterol?

A

LDL receptors

43
Q

What can be deduced by the fact that in LDL-R negative patients, macrophages continued to accumulate cholesterol?

A

The presence of scavenger receptors - that are unresponsive to negative feedback facilitated by the continued intake of oxidised LDL.

44
Q

What are the functions of macrophage scavenger receptor A (CD204)?

A

Binds to oxidised LDL

Binds to gram positive bacteria (staphylococci and streptococci)

Binds to dead cells

45
Q

Which type of macrophage scavenger receptor binds to malaria parasites?

A

MSRB (CD-36)

46
Q

What are the functions of macrophage scavenger receptor B?

A
  • Binds to oxidised LDL
  • Binds to malaria parasites
  • Binds to dead cells.
47
Q

Which oxidative enzymes are released by macrophages, that can modify native LDL?

A

NADPH oxidase (superoxide O2)

Myeloperoxidase

48
Q

Which types of molecules are upregulated by IL-1?

A

VCAM-I

Vascular cell adhesion molecule-1

49
Q

What is the function of VCAM-I?

A

Mediates tight monocyte binding involves in recruitment

50
Q

Which type of chemokine is released by activated macrophages that recruits monocyte?

A

Monocyte chemotactic protein-I MCP-I

51
Q

Which type of receptors does MCP-I bind onto?

A

Monocyte G-protein coupled receptor CCR2

52
Q

What are the effects of macrophage derived growth factors?

A

Recruit vascular smooth muscle and promote proliferation to deposit extracellular matrix.

53
Q

Which types of growth factors are released by macrophages?

A

1) Platelet derived growth factor (PDGF)

2) Transforming growth factor beta (TGF-b)

54
Q

What is the function of PDGF?

A

Support VSMC chemotaxis, survival and promote cell division.

55
Q

What is the function of TGF-b?

A

Increases collagen synthesis and matrix deposition.

56
Q

What is the effect on VSMCs by interactions of PDGF and TGF-b?

A

Contractile smooth conversion to synthetic atherosclerotic cells with reduced contractile filaments and an increase in matrix deposition genes

57
Q

What are the two differences between normal medial contractile and synthetic atherosclerotic cells?

A

Decreased contractile filaments

And increase in matrix deposition genes

(In Synthetic)

58
Q

Which type of proteinases are released by macrophages?

A

Metalloproteinases

59
Q

What is the function of metalloproteinases released by macrophages?

A

Responsible for forming a proteolytic cascade to degrade collagen, requiring zinc in the active site

60
Q

Which ion is involved in metalloproteinases?

A

Zinc

61
Q

What are the impacts of metalloproteinases on the fibrous cap?

A

Potentiates thin fibrous cap degradation, increasing the susceptibility of plaque rupture

Rupture promotes coagulation - occlusive thrombus and cessation of blood flow

62
Q

What is the consequence of a thin fibrous cap rupture by metalloproteinase activity?

A

Causes the release of necrotic foam debris into the arterial lumen, this initiates thrombosis that ultimately causes an infarction

63
Q

Which OxLDL derived metabolite is toxic?

A

7-keto-cholesterol

64
Q

Which transcription factor regulates inflammation and is activated by numerous inflammatory stimuli?

A

Nuclear kappa B

65
Q

Which receptors are expressed by nuclear kappa B?

A

Scavenger receptors
Toll-like receptors
Cytokine receptors (IL-1)

66
Q

Nuclear kapp B activates the gene expression of what in macrophages?

A

MMPs, Inducible nitric oxide synthase and interleukin - implicated in inflammation

67
Q

What are the risk factors of athersclerosis?

A 
Smoking
Hypertension 
Diabetes
Hyperlipidemia
Localised disturbed flow

Y2 BRS (Haroop) (62 decks)

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